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New potent vaccine against brucellosis based on multi-epitope prediction method of inf C protein. In silico study
Nueva y potente vacuna contra la brucelosis, basada en un método de predicción de múltiples epítopos de la proteína inf C. Estudio in silico
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"documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Vacunas. 2024;25:152-60" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Effectiveness of the vaccine (Covaxin®) on different age groups of people: A pilot study" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "152" "paginaFinal" => "160" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Efectividad de la vacuna (Covaxin®) en los diferentes grupos de edad de las personas: Estudio piloto" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1028 "Ancho" => 3153 "Tamanyo" => 252421 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Optimized dilution of Ab-HRP conjugate for different age groups of samples (such as 21–30, 31–40, 41–50, 51–60, and 61–70 years of age). Statistics <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.05 is only considered as significant (One-way ANOVA). 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Estudio <span class="elsevierStyleItalic">in silico</span>" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0055" "etiqueta" => "Fig. 11" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr11.jpeg" "Alto" => 2278 "Ancho" => 2008 "Tamanyo" => 341777 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0055" "detalle" => "Fig. 1" "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0055" class="elsevierStyleSimplePara elsevierViewall">The immune cells in various states. (a) B cell isotypes, (b) T helper cell isotypes, (c) T cytotoxic isotypes, (d) natural killer cell population, (e) macrophage population, and (f) dendritic cells.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Brucellosis is an important zoonotic disease caused by certain intracellular <span class="elsevierStyleItalic">Brucella</span> species. Its pathogenic effect depends on the zoonotic potential and host origins.<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleItalic">Brucella melitensis</span> (<span class="elsevierStyleItalic">B. melitensis</span>), <span class="elsevierStyleItalic">B. abortus</span>, and <span class="elsevierStyleItalic">B. suis</span> are the most human pathogens with significant clinical symptoms.<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a> Brucellosis disease could be found in the Mediterranean geographic zone regions, South America, the Middle East, and Latin America in which it causes vast economic loss due to animal abortion, reproductive failure, and decreased milk.<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> In addition to this, inhaling aerosolized bacteria or ingesting contaminated food by humans induce undulant fever, prostatitis, spondylitis, encephalitis, orchitis, arthritis, endocarditis, meningitis, and weakness.<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">The identification of virulence factors for <span class="elsevierStyleItalic">Brucella</span> usually depends on a large-scale screening and testing in model systems, because species in this genus, like other members of Proteobacteria class, don’t express the classical bacterial virulence factors like plasmids, fimbriae, pili, adhesins, and toxins but they colonize eukaryotic cells in a pathogenic/symbiotic relationship.<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> Indeed after the initial contact between <span class="elsevierStyleItalic">Brucella</span> and the host cell; which occurs obviously between the bacterial cell surface and the cellular plasma membrane, <span class="elsevierStyleItalic">Brucella</span> species multiply and deploy several strategies to survive into their host cells.<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">Recently, the LPS O-polysaccharide (O-PS) was shown to play an important role in the inhibition of phagocytosis and the bacterial killing factors inside the phagolysosome besides their role in stopping host cell apoptosis. The O-PS is the first molecule clearly shown to be involved in <span class="elsevierStyleItalic">Brucella</span> intracellular entry and defense against the bactericidal cationic peptides and polycations host cellular lysis factors, or against the humoral defense via the complement-mediated lysis.<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a> It is also clear that <span class="elsevierStyleItalic">Brucella</span> LPS acts as an immunomodulator for protein antigen presentation of MHC class II molecules.</p><p id="p0020" class="elsevierStylePara elsevierViewall">In addition to LPS and O-PS effectors, the type IV secretion system encoded by the operon virB (virB T4SS) is a major virulence factor of <span class="elsevierStyleItalic">Brucella</span> because it is involved in the recruitment of lipid rafts for entry of <span class="elsevierStyleItalic">Brucella</span> species into macrophages or to reach their proper niches in which they replicate. For all these reasons, vaccination must be used to prevent humans from Brucellosis. In general, inactivated vaccines confer relatively low levels of protection because these kinds of vaccines are developed on basis of the attenuation principle which is achieved by growing the pathogen in abnormal conditions for long durations. But sometimes, a failure in the inactivation or killing of the pathogenic organism could lead to disease outbreak upon vaccination. This is the reason why that other strategies have been developed in particular those based on using parts of the organism in vaccines designing. Currently, effective vaccines were designed from antigens to direct immune responses induction and strong protections from many pathogens like <span class="elsevierStyleItalic">Brucella</span> were obtained using vectored vaccines, DNA vaccines, reverse genetics-engineered live-attenuated vaccines, or multi-epitope vaccines.<a class="elsevierStyleCrossRefs" href="#bb0040"><span class="elsevierStyleSup">8–12</span></a> The epitope-based vaccines are considered to be safer than traditional vaccines and focus on the most crucial antigenic elements of the pathogen which could stimulate both cellular and humoral immunity without allergenic and toxic properties.<a class="elsevierStyleCrossRefs" href="#bb0065"><span class="elsevierStyleSup">13–16</span></a> Also through the <span class="elsevierStyleItalic">in silico</span> vaccines designing methods, suitable adjuvants with a strong immunostimulatory potential such as inducing DC maturation and T-helper cell responses are used.<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a> Then, the selected epitopes and adjuvants are jointed to adequate linkers with reduced junctional immunogenicity like AAY and GPGPG linkers and the C N-terminal regions are usually inserted to EAAAK linker into the <span class="elsevierStyleItalic">in silico</span> vaccine construct to avoid its interaction with other regions.<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a> So, the objective of this study is to design a peptide vaccine from <span class="elsevierStyleItalic">Brucella</span> components which include multivalent B- and T cell epitopes to elicit high humoral and cell immunity responses to prevent <span class="elsevierStyleItalic">Brucella</span> infection. So, in this work, a multi-epitope vaccine with a total of 1 BCL epitope, 11 CTL epitopes, and 38 HTL epitopes from <span class="elsevierStyleItalic">Brucella inf</span> C protein combined with appropriate linkers and adjuvant was designed using bioinformatics tools <a class="elsevierStyleCrossRef" href="#f0005">Fig. 1</a>.</p><elsevierMultimedia ident="f0005"></elsevierMultimedia></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Materials and methods</span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Retrieval of targeted amino acid sequences</span><p id="p0025" class="elsevierStylePara elsevierViewall">The amino acid sequences of the targeted protein on <span class="elsevierStyleItalic">Brucella inf</span> C were retrieved from the Uniprot database and aligned by ClustalW. The aligned file was visualized by the webserver ESPript (<a href="https://espript.ibcp.fr/ESPript/cgi-bin/ESPript.cgi">https://espript.ibcp.fr/ESPript/cgi-bin/ESPript.cgi</a>), then the conserved region was selected by BioEdit software to use it for further analysis after antigenic detection by Vaxijen v2.0 (<a href="http://www.ddg-pharmfac.net/vaxijen/">http://www.ddg-pharmfac.net/vaxijen/</a>).<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a></p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">T- and B cell epitopes prediction</span><p id="p0030" class="elsevierStylePara elsevierViewall">The Immune Epitope Database (IEDB) (<a href="https://www.iedb.org/">https://www.iedb.org/</a>)<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a> was used to predict linear B-cell epitopes using the BepiPred linear epitope method. The MHC class-I restricted CD8<span class="elsevierStyleSup">+</span> cytotoxic T-lymphocyte (CTL) epitopes of the selected sequences were obtained using the Net MHCpan EL 4.1 prediction method for HLA-A*01-01 allele, keeping the sequence length 9. The MHC class-II restricted CD4þ helper T-lymphocyte (HTL) epitopes were obtained for HLA DRB1*01-01 allele by using IEDB Recommende Method 2.2. These 2 alleles were selected according to Li et al.,<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a> and Tarrahimofrad et al., 19.</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Antigenicity, toxicity, and allergenicity prediction</span><p id="p0035" class="elsevierStylePara elsevierViewall">The antigenicity, allergenicity, and toxicity prediction of the selected epitopes was evaluated by Vaxijen v2.0 (<a href="http://www.ddg-pharmfac.net/vaxijen/">http://www.ddg-pharmfac.net/vaxijen/</a>),<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> Allergen FP v1.0 (<a href="https://www.ddg-pharmfac.net/AllerTOP/">https://www.ddg-pharmfac.net/AllerTOP/</a>),<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> and ToxinPred (<a href="http://crdd.osdd.net/raghava/toxinpred/">http://crdd.osdd.net/raghava/toxinpred/</a>),<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a> respectively. The antigenic, non-allergenic, and non-toxic epitopes were selected for vaccine construction.</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Vaccine construction and toxicity prediction</span><p id="p0040" class="elsevierStylePara elsevierViewall">For vaccine construction, the best selected CTL, HTL, and BCL epitopes were combined together (antigenic, non-allergenic, and non-toxic). The N-terminal position of the designed vaccine was linked with a sequence of 125 amino acids residue of the 50S ribosomal L7/L12 peptide, which acts as an adjuvant. EAAAK linker was used to conjugate the adjuvant and BCL epitope, GPGPG was used to conjugate BCL with HTL epitopes, and AAY was used to conjugate HTL with CTL and CTL with CTL epitopes. This linear structure was subjected to toxicity prediction using CSM-Toxin<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> and Toxinpred2<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a> webservers.</p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Vaccine tertiary structure prediction, refinement, and verification</span><p id="p0045" class="elsevierStylePara elsevierViewall">The vaccine protein tertiary structure was obtained using phyre 2 web server (<a href="http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id=index">http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id=index</a>)<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a> and refined by galaxy webserver (<a href="http://galaxy.seoklab.org/">http://galaxy.seoklab.org/</a>).<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a> The 3D structure of the vaccine constructed was visualized by Discovery Studio Visualizer. The vaccine protein was then validated by analyzing the Ramachandran plot generated using the online server PROCHECK (<a href="https://saves.mbi.ucla.edu/">https://saves.mbi.ucla.edu/</a>).<a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a> The Z-score of the 3D structure was analyzed by the ProSA webserver (<a href="https://prosa.services.came.sbg.ac.at/prosa.php">https://prosa.services.came.sbg.ac.at/prosa.php</a>)<a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a> and the overall quality factor of the final model was checked using ERRAT program (<a href="https://saves.mbi.ucla.edu/">https://saves.mbi.ucla.edu/</a>).</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Protein–protein docking</span><p id="p0050" class="elsevierStylePara elsevierViewall">In protein–protein docking, the binding affinities of the constructed vaccine were analyzed by docking with various MHC alleles and TLRs. The vaccine was docked with 4 selected MHC alleles to test their binding affinity, i.e., DRB1*0101 (PDB ID: 2FSE), DRB3*0202 (PDB ID: 1A6A), HLA-A*11:01 (PDB ID: 5wjl), and HLA-DRB1*04:01(PDB ID: 5jlz<span class="elsevierStyleBold">)</span>. In addition, the designed vaccine was also docked with TLR-8 (PDB ID: 3W3M) and TLR-3 (PDB ID: 2A0Z). The docking was carried out by ClusPro 2.0.<a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a> The best docking result was analyzed by LigPlot<span class="elsevierStyleHsp" style=""></span>+ software and complexes with better binding affinity (the lower energy score) determined by prodigy server was considered to carry out for further analysis.</p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0105">Molecular dynamics simulation</span><p id="p0055" class="elsevierStylePara elsevierViewall">The molecular dynamic simulation was performed using the GROMACS package<a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a> integrated in WebGRO for Macromolecular Simulations (<a href="https://simlab.uams.edu/">https://simlab.uams.edu/</a>) to complexes stabilities analysis. Parameters like root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and the number of complex H-bonds were calculated. <a href="http://davapc1.bioch.dundee.ac.uk/cgi-bin/prodrg">http://davapc1.bioch.dundee.ac.uk/cgi-bin/prodrg</a>. The simulation was performed in a triclinic water box with SPC water model electro-neutralized by addition of 0.15 M NaCl with an energy minimization of the system of 5000 steps by the steepest descent algorithm. The solvent around proteins equilibration was conducted through NVT/NPT ensembles at a constant temperature of 300 K and constant pressure of 1.0 bar. The MD was run for a time of 50 ns.</p></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0110">Codon adaptation and <span class="elsevierStyleItalic">in silico</span> cloning</span><p id="p0060" class="elsevierStylePara elsevierViewall">Before the designed vaccine sequence cloning, a codon adaptation evaluation in <span class="elsevierStyleItalic">E</span>. <span class="elsevierStyleItalic">coli</span> k-12 was performed by JCat server (<a href="http://www.jcat.de/">http://www.jcat.de/</a>)<a class="elsevierStyleCrossRef" href="#bb0155"><span class="elsevierStyleSup">31</span></a> to ensure an efficient and a better production of the desired product. After that, the Pdraw 32 software was used to insert the newly adapted DNA sequences between the SgrA1 and SphI restriction sites of the Pet19b(+) vector.</p></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0115">Immune response simulation</span><p id="p0065" class="elsevierStylePara elsevierViewall">The immune response profile of the generated vaccine candidates was evaluated by C-IMMSIM server (<a href="http://150.146.2.1/C-IMMSIM/index.php">http://150.146.2.1/C-IMMSIM/index.php</a>). After uploading sequences of the designed vaccine, simulation was performed at a random speed, simulation volume, and simulation steps of 12 345, 50, and 1100 respectively. Three <span class="elsevierStyleItalic">in silco</span> injections were given at the time steps of 1, 84, and 168, respectively (1-time step is equal to 8 h in real life), with no LPS and maintained minimum 30 days of time interval between 2 injections.</p></span></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0120">Results and discussion</span><p id="p0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Brucellocis</span> is a zoonotic disease with a high incidence and prevalence worldwide. This pathogenesis is mainly based on the <span class="elsevierStyleItalic">Brucella abortus</span> ability to survive and multiply into the host cells. Generally, the host colonization conducts to morbidity.<a class="elsevierStyleCrossRef" href="#bb0160"><span class="elsevierStyleSup">32</span></a> So, the vaccination is considered to be the most effective measure to prevent these infectious diseases. However, at the moment, very few vaccine candidates are described for Brucellosis because as explained above<span class="elsevierStyleItalic">,</span> difficulties with the proper cultivation of this intracellular microbe and the cattle abortions of pregnant animal caused by some vaccine have usually compromised the development of efficient vaccines against Brucellosis. Moreover, the vaccine elaboration on basis of the conventional approaches is expensive and time-consuming. Immunoinformatic tools could facilitate and accelerate the multiepitope vaccine designing because the toxic, the allergenic, and the non-antigenic parts of an antigen can be eliminated during a vaccine designing in an <span class="elsevierStyleItalic">in silico</span> study.<a class="elsevierStyleCrossRef" href="#bb0165"><span class="elsevierStyleSup">33</span></a> In the present study, an <span class="elsevierStyleItalic">in silico</span> based methods were exploited to design a potential vaccine against <span class="elsevierStyleItalic">Brucella</span> from peptides sequences which act as ligands.</p><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0125">Sequence retrieval, antigenicity, and toxicity prediction</span><p id="p0075" class="elsevierStylePara elsevierViewall">Many vaccine subunit were developed by using macromolecules like protein which could induce protective immunity.<a class="elsevierStyleCrossRef" href="#bb0170"><span class="elsevierStyleSup">34</span></a> For this reason, in the present study, the conserved region for vaccine designing was selected from sequences already retrieved from the UniProt database and aligned by ClustalW (<a class="elsevierStyleCrossRef" href="#f0010">Fig. 2</a>). After that, the antigenicity analysis of the conserved region has been predicted by the Vaxijen webserver. The antigenicity of a molecule is determined when the B- or T cell receptors were defined as an antigen.<a class="elsevierStyleCrossRef" href="#bb0170"><span class="elsevierStyleSup">34</span></a> Results showed that the conserved region of <span class="elsevierStyleItalic">Brucella inf</span> C protein sequence is VKMKAAQRFFEEGDKVKVTLRFRGREMAHQELGMKLLRVKEDTVEIAKVESEPKLEGRQMMMVLAPR which shows an antigenicity score of 0.6410.</p><elsevierMultimedia ident="f0010"></elsevierMultimedia></span><span id="s0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0130">Multi-epitope vaccine construction and toxicity prediction</span><p id="p0080" class="elsevierStylePara elsevierViewall">To stimulate the cytotoxic T cells, helper T cells, and B cells in immunogenic response an effective multi-epitope subunit vaccine should contain the CTL, HTL, and BCL epitopes.<a class="elsevierStyleCrossRef" href="#bb0165"><span class="elsevierStyleSup">33</span></a> The vaccine should be also able to provoke a potential immune response.<a class="elsevierStyleCrossRef" href="#bb0170"><span class="elsevierStyleSup">34</span></a> However, the <span class="elsevierStyleItalic">in silico</span> analysis by the IEDB server generated a lot of possible epitopes, so some special criteria like to be antigenic to strong immune response induction and to not produce any harmful, toxic, and allergenic reaction within the body are set for the final selection of the best epitopes which will be used in vaccine construction.<a class="elsevierStyleCrossRef" href="#bb0170"><span class="elsevierStyleSup">34</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0175"><span class="elsevierStyleSup">35</span></a> The development of a vaccine subunit needs also the selection of appropriate linkers and adjuvant. In the case of the present work, the designed vaccine maintained the sequence MHC class-I epitopes, MHC class-II epitopes, and B cell epitopes along with appropriate linkers (EAAAK, GPGPG, and AAY) at the appropriate positions and a 50S ribosomal protein adjuvant (a sequence of 125 amino acids residue of the 50S ribosomal L7/L12 peptide) at the N-terminal position. The adjuvant was employed to increase the chimeric vaccine’s efficiency and boost the immune responses.<a class="elsevierStyleCrossRef" href="#bb0180"><span class="elsevierStyleSup">36</span></a> The efficacy of the 50S ribosomal protein L7/L12 from <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> as a natural immunoadjuvant to induce dendritic and normal T cells, has been reported in many previous studies including <span class="elsevierStyleItalic">in-silico</span> approaches for designing vaccine candidates against <span class="elsevierStyleItalic">Brucella melitensis</span>, <span class="elsevierStyleItalic">B. suis</span>, and <span class="elsevierStyleItalic">B. abortus.</span><a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0185"><span class="elsevierStyleSup">37</span></a> Therefore, this TLR4 agonist was added to 1 BCL epitope, 11 CTL epitopes, and 38 HTL epitopes (<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>) to design a linear vaccine. The predicted B-cell and helper epitopes were joined each one to the other using GPGPG linkers, HTL were conjugated to CTL epitopes with AAY linker and the adjuvant to BCL epitope by EAAAK linker. These linkers help in the prevention of potential junctional epitopes, facilitate also the immune processing in addition to act as a rigid spacer between the protein domains.<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0170"><span class="elsevierStyleSup">34</span></a> The resulted vaccine sequence is: MAKLSTDELLDAFKEMTLLELSDFVK KFEETFEVTAAAPVAVAAAGAAPAGAAVEAAEEQSEFDVILEAAGD KKIGVIKVVREIVSGLGLKEAKDLVDGAPKPLLEKVAKEAADEAKAKLEAAGATVTVKEAAAKVEIAKVESEPKLEGRGPGPGEMAHQELGMKLLQRVAAYVTLRFRGREMAHQELAAYKVTLRFRGREMAHQEAAYVKVTLRFRGREMAHQAAYPKLEGRQMMMVLAPRAAYFRGREMAHQELGMKLAAYEPKLEGRQMMMVLAPAAYGREMAHQELGMKLLQAAYLRFRGREMAHQELGMAAYREMAHQELGMKLLQRAAYRGREMAHQELGMKLLAAYSEPKLEGRQMMMVLAAAYKVKVTLRFRGREMAHAAYRFRGREMAHQELGMKAAYDKVKVTLRFRGREMAAAYGDKVKVTLRFRGREMAAYEDTVEIAKVESEPKLAAYEGDKVKVTLRFRGREAAYKEDTVEIAKVESEPKAAYEEGDKVKVTLRFRGRAAYDTVEIAKVESEPKLEAAYTVEIAKVESEPKLEGAAYVEIAKVESEPKLEGRAAYESEPKLEGRQMMMVLAAYFEEGDKVKVTLRFRGAAYFFEEGDKVKVTLRFRAAYQRFFEEGDKVKVTLRAAYRFFEEGDKVKVTLRFAAYAAQRFFEEGDKVKVTAAYKAAQRFFEEGDKVKVAAYVESEPKLEGRQMMMVAAYEIAKVESEPKLEGRQAAYIAKVESEPKLEGRQMAAYRVKEDTVEIAKVESEAAYVKEDTVEIAKVESEPAA YQRVKEDTVEIAKVESAAYKVESEPKLEGRQMMMAAYAKVESEP KLEGRQMMAAYKVESEPKLAAYMAHQELGMAAYSEPKLEGRAAYEEGDKVKVAAYFEEGDKVKAAYLRFRGREMAAYVESEPKLEAAYIAKVESEP AAYVKMKAAQRAAYQMMMVLAPAAYAKVESEPK</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0085" class="elsevierStylePara elsevierViewall">Examination of the safety and the chemical properties of the designed structure using both CSM-toxin and toxinpred2 servers showed that the molecular weight of the vaccine structure is 100 966.8 daltons with a net charge of 11.25. These make it an acceptable vaccine with a molecular weight suitable for vaccine production.<a class="elsevierStyleCrossRef" href="#bb0190"><span class="elsevierStyleSup">38</span></a> The total number of aliphatic, non-polar, charged, polar, and aromatic amino acids are 301, 509, 314, 388, and 88, respectively, with a hydrophobicity index of -0.45 which indicates that the vaccine structure is hydrophilic and has a good interaction with water molecules<a class="elsevierStyleCrossRef" href="#bb0195"><span class="elsevierStyleSup">39</span></a> (<a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>).</p></span><span id="s0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0135">3D structure prediction and validation</span><p id="p0090" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#f0015">Fig. 3</a> shows the 3D protein's structure before and after refinement, as visualized by discovery BIOVIA. The quality of all fusion construct models was determined by ERRAT, Ramachandran plot, and ProSA-Web tools. Based on the validation results, the Ramachandran plot of the model structure shows the most of the residues (95.6% of the residues) clustered in the favored region, 3.5% in extra allowed regions, and 0.9% in disallowed regions (<a class="elsevierStyleCrossRef" href="#f0020">Fig. 4</a>A). In addition, the generated Z-score of the 3D model was found to be −<span class="elsevierStyleHsp" style=""></span>5.33, as predicted by the ProSA-Web server (<a class="elsevierStyleCrossRef" href="#f0020">Fig. 4</a>B) which indicates that the model need no refinement and the protein belongs to the plot of Z-scores of previously identified structures solved by NMR and X-ray crystallographic experiments. In ERRAT server, the overall quality factor of the final protein model was 99.16% notably higher than the limit value of 95% which indicated here also high resolution of structures (<a class="elsevierStyleCrossRef" href="#f0020">Fig. 4</a>C). All these analyses support the overall quality of the vaccine model.</p><elsevierMultimedia ident="f0015"></elsevierMultimedia><elsevierMultimedia ident="f0020"></elsevierMultimedia></span><span id="s0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0140">Protein–protein docking</span><p id="p0095" class="elsevierStylePara elsevierViewall">The ClusPro 2.0 server docking results are shown in the <a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>. The lowest energy score corresponds to the better binding affinity. The position of the best docked design was visualized by discovery BIOVIA (<a class="elsevierStyleCrossRef" href="#f0025">Fig. 5</a>) and interactions were analysed by Ligplot<span class="elsevierStyleHsp" style=""></span>+ (<a class="elsevierStyleCrossRef" href="#f0030">Fig. 6</a>). The docking study revealed binding energies of −12.8 kcal/mol, −11.8 kcal/mol, −10.6 kcal/mol, −9.8 kcal/mol, −10.0 kcal/mol, and −8.8 kcal/mol between vaccine and TLR-8, DRB3*0202, DRB1*04:01, HLA-A*11:01, DRB1*0101, and TLR-3 respectively indicating highest binding scores with the most negative binding energy (<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>) and strong interactions (<a class="elsevierStyleCrossRef" href="#f0030">Fig. 6</a>) between vaccine construct and TLR-8. This complex was selected for further analysis.</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="f0025"></elsevierMultimedia><elsevierMultimedia ident="f0030"></elsevierMultimedia><elsevierMultimedia ident="t0015"></elsevierMultimedia></span><span id="s0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0145">Molecular dynamics simulation</span><p id="p0100" class="elsevierStylePara elsevierViewall">The conformational stability of the best-docked complex vaccine-TLR-8 was investigated using molecular dynamics simulation analysis. Parameters like RMSD, RMSF, hydrogen bonds, and Rg were calculated to appreciate the changes in the stability of the protein as induced after binding. SASA was further analyzed to elucidate the change in the solvent accessibility in the proteins. After the first 10 ns, the movement of RMSD is relatively less with values ranging between 4.5 and 5 Å (<a class="elsevierStyleCrossRef" href="#f0035">Fig. 7</a>a). Less deviations were also noted in the RMSF trajectory inferring stability of the newly designed vaccine-TLR8 complex (<a class="elsevierStyleCrossRef" href="#f0035">Fig. 7</a>b). H-bonds contribute significantly in stabilizing the protein. As indicated in <a class="elsevierStyleCrossRef" href="#f0035">Fig. 7</a>c, more than 650 h-bonds were displayed in the vaccine–TLR8 complex confirming the rigid conformation of this complex. Further, the Rg was analyzed to appreciate the compactness of the protein after binding. From the figure (<a class="elsevierStyleCrossRef" href="#f0035">Fig. 7</a>d), it can be seen that the Rg plot decreased, then stabilized at a value of 3.05 nm after the first 10 ns time period. This indicates more compactness and stability in protein’s structural conformation after binding. A decrease in SASA value was also noted (<a class="elsevierStyleCrossRef" href="#f0035">Fig. 7</a>e) confirming the loss of solvent molecules after the protein folding.</p><elsevierMultimedia ident="f0035"></elsevierMultimedia></span><span id="s0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0150">Codon adaptation and <span class="elsevierStyleItalic">in silico</span> cloning</span><p id="p0105" class="elsevierStylePara elsevierViewall">The development of DNA vaccines involves the cloning of a gene for an antigenic protein in a plasmid,<a class="elsevierStyleCrossRef" href="#bb0175"><span class="elsevierStyleSup">35</span></a> the Java Codon Adaptation Tool was used to check codon adaptation of vaccine candidates in system expression of <span class="elsevierStyleItalic">Escherichia coli</span> strain k12. This server estimated the optimized sequence’s GC content to be 50.73% its Codon Adaptation Index (CAI) value to be 1.0 (<a class="elsevierStyleCrossRef" href="#f0040">Fig. 8</a>). It revealed also that the constructed multi-epitope vaccine is composed of 2871 nucleotides.</p><elsevierMultimedia ident="f0040"></elsevierMultimedia><p id="p0110" class="elsevierStylePara elsevierViewall">Before cloning into <span class="elsevierStyleItalic">E. coli</span> strain K12, the vaccine DNA sequence was inserted within the SgrAI and SphI restriction sites on pET-19b plasmid vectors in pDRAW32 software for expression and production of the desired vaccine in <span class="elsevierStyleItalic">E. coli</span> cells. This insertion resulted in combined plasmids of 8435 pb. Results illustrated in <a class="elsevierStyleCrossRef" href="#f0045">Fig. 9</a> showed that the combined plasmid could be cloned into the <span class="elsevierStyleItalic">E. coli</span> cells with successfully vaccine production. This vaccine can be injected into the host which takes up the DNA and expresses the protein to induce protective immunity.<a class="elsevierStyleCrossRef" href="#bb0200"><span class="elsevierStyleSup">40</span></a></p><elsevierMultimedia ident="f0045"></elsevierMultimedia></span><span id="s0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0155">Immune response simulation</span><p id="p0115" class="elsevierStylePara elsevierViewall">After 3 <span class="elsevierStyleItalic">in silico</span> injections of the designed vaccine as indicated above, the results of C-IMM SIM online server revealed a primary followed by strong secondary and tertiary immune responses. In first high concentrations of IgM, and IgM<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>IgG were noted (<a class="elsevierStyleCrossRef" href="#f0050">Fig. 10</a>), then a continual increase level of total IgM<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>IgG, IgG1<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>IgG2 antibodies with rapid decrease in antigen concentration were depicted after the two last doses of vaccine (<a class="elsevierStyleCrossRef" href="#f0050">Fig. 10</a>). This humoral immune response was accompanied by a considerable increase in the number of B cells in particular of B memory (y2) subpopulations (<a class="elsevierStyleCrossRef" href="#f0055">Fig. 11</a>a), and T cells in particular of T helper (Th), Th memory (y2), (<a class="elsevierStyleCrossRef" href="#f0055">Fig. 11</a>b) and cytotoxic T cells (<a class="elsevierStyleCrossRef" href="#f0055">Fig. 11</a>c). Other immune cells activities were stimulated by the construct vaccine like the natural killer (<a class="elsevierStyleCrossRef" href="#f0055">Fig. 11</a>d), macrophage (<a class="elsevierStyleCrossRef" href="#f0055">Fig. 11</a>e), and dendritic cells (<a class="elsevierStyleCrossRef" href="#f0055">Fig. 11</a>f). Finally, increased cytokine and interleukine productions were also observed (<a class="elsevierStyleCrossRef" href="#f0060">Fig. 12</a>).</p><elsevierMultimedia ident="f0050"></elsevierMultimedia><elsevierMultimedia ident="f0055"></elsevierMultimedia><elsevierMultimedia ident="f0060"></elsevierMultimedia></span></span><span id="s0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0160">Conclusion</span><p id="p0120" class="elsevierStylePara elsevierViewall">In the current study, a vaccinomic approach was used to design a new vaccine against Brucellosis. The conserved region of <span class="elsevierStyleItalic">inf</span> C protein was found to be an ideal way to use it for epitopes prediction. These epitopes with a suitable adjuvant were conjugated each one to the other using linkers to generate an effective vaccine that gives a good binding affinity with various MHC alleles and TLRs. The subunit vaccine was successfully cloned into <span class="elsevierStyleItalic">E. coli</span> cells. The construct vaccine induces a high immune response <span class="elsevierStyleItalic">in silico</span>, however further <span class="elsevierStyleItalic">in vivo</span> and <span class="elsevierStyleItalic">in vitro</span> experiments might be required to validate these study findings.</p></span><span id="s2100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st2160">Confict of interest</span><p id="p2120" class="elsevierStylePara elsevierViewall">The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.</p></span><span id="s3100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st3160">Funding</span><p id="p3120" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres2141537" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "as0005" "titulo" => "Purpose" ] 1 => array:2 [ "identificador" => "as0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "as0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "as0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1818096" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2141536" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "as0025" "titulo" => "Propósito" ] 1 => array:2 [ "identificador" => "as0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "as0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "as0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1818095" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "s0010" "titulo" => "Materials and methods" "secciones" => array:9 [ 0 => array:2 [ "identificador" => "s0015" "titulo" => "Retrieval of targeted amino acid sequences" ] 1 => array:2 [ "identificador" => "s0020" "titulo" => "T- and B cell epitopes prediction" ] 2 => array:2 [ "identificador" => "s0025" "titulo" => "Antigenicity, toxicity, and allergenicity prediction" ] 3 => array:2 [ "identificador" => "s0030" "titulo" => "Vaccine construction and toxicity prediction" ] 4 => array:2 [ "identificador" => "s0035" "titulo" => "Vaccine tertiary structure prediction, refinement, and verification" ] 5 => array:2 [ "identificador" => "s0040" "titulo" => "Protein–protein docking" ] 6 => array:2 [ "identificador" => "s0045" "titulo" => "Molecular dynamics simulation" ] 7 => array:2 [ "identificador" => "s0050" "titulo" => "Codon adaptation and in silico cloning" ] 8 => array:2 [ "identificador" => "s0055" "titulo" => "Immune response simulation" ] ] ] 6 => array:3 [ "identificador" => "s0060" "titulo" => "Results and discussion" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "s0065" "titulo" => "Sequence retrieval, antigenicity, and toxicity prediction" ] 1 => array:2 [ "identificador" => "s0070" "titulo" => "Multi-epitope vaccine construction and toxicity prediction" ] 2 => array:2 [ "identificador" => "s0075" "titulo" => "3D structure prediction and validation" ] 3 => array:2 [ "identificador" => "s0080" "titulo" => "Protein–protein docking" ] 4 => array:2 [ "identificador" => "s0085" "titulo" => "Molecular dynamics simulation" ] 5 => array:2 [ "identificador" => "s0090" "titulo" => "Codon adaptation and in silico cloning" ] 6 => array:2 [ "identificador" => "s0095" "titulo" => "Immune response simulation" ] ] ] 7 => array:2 [ "identificador" => "s0100" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "s2100" "titulo" => "Confict of interest" ] 9 => array:2 [ "identificador" => "s3100" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "xack743296" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-06-09" "fechaAceptado" => "2023-10-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1818096" "palabras" => array:6 [ 0 => "<span class="elsevierStyleItalic">Brucella</span>" 1 => "Vaccine" 2 => "<span class="elsevierStyleItalic">Inf</span> C" 3 => "<span class="elsevierStyleItalic">In silico</span>" 4 => "Epitopes" 5 => "Simulation" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1818095" "palabras" => array:6 [ 0 => "Brucella" 1 => "Vacuna" 2 => "<span class="elsevierStyleItalic">Inf</span> C" 3 => "<span class="elsevierStyleItalic">In silico</span>" 4 => "Epítopos" 5 => "Simulación" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Purpose</span><p id="sp0080" class="elsevierStyleSimplePara elsevierViewall">Brucellosis infection could be eradicated by using an effective vaccine. <span class="elsevierStyleItalic">Inf</span> C gene expression generates one of the main <span class="elsevierStyleItalic">Brucella</span> pathogenesis proteins. The purpose of this study was to design a new vaccine against <span class="elsevierStyleItalic">Brucella</span> disease by <span class="elsevierStyleItalic">in silico</span> determination of epitopes of <span class="elsevierStyleItalic">inf</span> C protein.</p></span> <span id="as0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Methods</span><p id="sp0085" class="elsevierStyleSimplePara elsevierViewall">In the first, <span class="elsevierStyleItalic">Inf</span> C amino acid sequences were extracted from the UniProt database and subjected to <span class="elsevierStyleItalic">in silico</span> analysis, including multiple sequence alignment, conserved region determination, allergenicity, antigenicity, and toxicity of the selected epitopes for TCL, HTL, and BCl. Vaccine-target (MHC alleles and TLRs) interactions, binding affinities, and dynamical stabilities were inspected through molecular docking and molecular dynamic simulation (MD) using Cluspro 2 server and GROMACS packages respectively. Further, the codon adaptation of the designed vaccine was determined by the JCat server and the obtained sequence was cloned in pET19b(+)vector by pDRAW32 software. Finally, the ability of the newer vaccine to stimulate the immune response was assessed using a computational immune simulation.</p></span> <span id="as0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Results</span><p id="sp0090" class="elsevierStyleSimplePara elsevierViewall">Results allowed us to select a peptide vaccine on basis of its good binding affinities with TLR-8 allele. The multi-peptide vaccine showed also to be highly antigenic, non-allergenic, non-toxic, and potential expression in <span class="elsevierStyleItalic">E coli</span>. Results showed also good stability of the vaccine–TLR8 complex and strong cellular and humoral immune response after three <span class="elsevierStyleItalic">in silico</span> injections of the vaccine construct.</p></span> <span id="as0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Conclusion</span><p id="sp0095" class="elsevierStyleSimplePara elsevierViewall">All these theoretical results reveal that the conserved region of <span class="elsevierStyleItalic">inf</span> C protein could be used for designing of a new potent vaccine against <span class="elsevierStyleItalic">Brucella</span>.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "as0005" "titulo" => "Purpose" ] 1 => array:2 [ "identificador" => "as0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "as0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "as0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="as0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Propósito</span><p id="sp0100" class="elsevierStyleSimplePara elsevierViewall">la infección por brucelosis podría erradicarse mediante el uso de una vacuna eficaz. La expresión del <span class="elsevierStyleItalic">Inf C</span> gen genera una de las principales proteínas de patogénesis de <span class="elsevierStyleItalic">Brucella</span>. El propósito de este estudio fue diseñar una nueva vacuna contra la enfermedad de <span class="elsevierStyleItalic">Brucella</span> mediante la determinación <span class="elsevierStyleItalic">in silico</span> de los epítopos de la <span class="elsevierStyleItalic">inf C</span> proteína.</p></span> <span id="as0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Métodos</span><p id="sp0105" class="elsevierStyleSimplePara elsevierViewall">En primer lugar, las secuencias de <span class="elsevierStyleItalic">Inf C</span> aminoácidos se extrajeron de la base de datos UniProt y se sometieron a análisis <span class="elsevierStyleItalic">in silico</span>, incluida la alineación múltiples de secuencias, la determinación de la región conservada, la alergenicidad, la antigenicidad y la toxicidad de los epítopos seleccionados para TCL, HTL y BCl. Las interacciones vacuna-objetivo (alelos MHC y TLR), afinidades de unión y estabilidades dinámicas se inspeccionaron mediante el acoplamiento molecular y molecular dinámica simulación (MD) utilizando el servidor Cluspro 2 y los paquetes GROMACS, respectivamente. Además, el servidor JCat determinó la adaptación de codones de la diseñada vacuna y luego la secuencia obtenida se clonó en el vector pET19b(+) mediante el software pDRAW32. Finalmente, se evaluó la capacidad de la nueva vacuna para estimular la respuesta inmunitaria mediante una computacional inmunitaria simulación.</p></span> <span id="as0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Resultados</span><p id="sp0110" class="elsevierStyleSimplePara elsevierViewall">los resultados nos permitieron de seleccionar una peptídica vacuna sobre la base de sus buenas afinidades de unión con el alelo TLR-8. La multipéptido vacuna demostró también ser altamente antigénica, no alergénica, no tóxica y con potencial expresión en <span class="elsevierStyleItalic">E coli</span>. Los resultados también mostraron una buena estabilidad del constructo complejo TLR8-vacuna y unas fuerte humoral y celular inmune respuestas después tres inyecciones <span class="elsevierStyleItalic">in silico</span> del constructa vacuna.</p></span> <span id="as0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Conclusión</span><p id="sp0115" class="elsevierStyleSimplePara elsevierViewall">Todos estos teóricos resultados revelan que la región conservada de la <span class="elsevierStyleItalic">inf C</span> proteína podría usarse para diseñar una nueva potente vacuna contra <span class="elsevierStyleItalic">Brucella</span>.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "as0025" "titulo" => "Propósito" ] 1 => array:2 [ "identificador" => "as0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "as0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "as0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:15 [ 0 => array:8 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 688 "Ancho" => 1181 "Tamanyo" => 84007 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Workflow of the overall methodology. In first amino acid sequences of the targeted protein were retrieved and aligned. Then, the conserved region was selected and analyzed for antigenic detection. After that the T- and B cell epitopes were identified and their antigenicity, toxicity, and allergenicity were predicted. Next, the vaccine was constructed, and its toxicity was predicted. Then, vaccine construct tertiary structure was predicted, refined, and verified. After that binding affinities of the constructed vaccine were analyzed by docking with various MHC alleles and TLRs before complexes stabilities analysis. Finally, the immune response profile of the generated vaccine candidates was evaluated after codon adaptation evaluation and in the <span class="elsevierStyleItalic">in silico</span> cloning of vaccine construct.</p>" ] ] 1 => array:8 [ "identificador" => "f0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2776 "Ancho" => 1315 "Tamanyo" => 1407968 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Amino acids sequence of <span class="elsevierStyleItalic">inf</span> C protein aligned by ClustalW and visualized by ESPript webserver.</p>" ] ] 2 => array:8 [ "identificador" => "f0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 635 "Ancho" => 1535 "Tamanyo" => 131729 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Vaccine 3D structure visualization by discovery studio tool. (A) Before refinement; (B) after refinement.</p>" ] ] 3 => array:8 [ "identificador" => "f0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 2059 "Ancho" => 945 "Tamanyo" => 145178 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">The vaccine tertiary structure prediction and verification. (A) The Procheck Ramachadran plot showing 95.6% of the residues in the favored region, 3.5% in extra allowed regions, and 0.9% in disallowed regions. (B) The Z score of −5.33 obtained with ProSa-Web. (c) The ERRAT overall quality factor of 99.16%.</p>" ] ] 4 => array:8 [ "identificador" => "f0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 681 "Ancho" => 945 "Tamanyo" => 112884 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0025" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">The 3D structure of vaccine–TLR-8 (TLR-8 in yellow) complex visualized by Discovery Studio BIOVIA.</p>" ] ] 5 => array:8 [ "identificador" => "f0030" "etiqueta" => "Fig. 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1154 "Ancho" => 2043 "Tamanyo" => 233102 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0030" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Docking interactions between vaccine (pink) and TLR-8 (brown) amino acids obtained by Ligplot<span class="elsevierStyleHsp" style=""></span>+.</p>" ] ] 6 => array:8 [ "identificador" => "f0035" "etiqueta" => "Fig. 7" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr7.jpeg" "Alto" => 1301 "Ancho" => 2008 "Tamanyo" => 164284 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0035" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">The molecular dynamic simulation of the docked complex vaccine-TLR8. (a) RMSD, (b) RMSF, (c) H-bonds, (d) Rg, and (e) SASA analysis.</p>" ] ] 7 => array:8 [ "identificador" => "f0040" "etiqueta" => "Fig. 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 884 "Ancho" => 1181 "Tamanyo" => 106766 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0040" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">Vaccine sequence adaptation by JCat server.</p>" ] ] 8 => array:8 [ "identificador" => "f0045" "etiqueta" => "Fig. 9" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr9.jpeg" "Alto" => 1266 "Ancho" => 2008 "Tamanyo" => 395716 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0045" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">In silico</span> restriction cloning of <span class="elsevierStyleItalic">Brucella</span> vaccine into pET-19b(+) vector using Pdraw32 software. The <span class="elsevierStyleItalic">Brucella</span> construct is shown in orange.</p>" ] ] 9 => array:8 [ "identificador" => "f0050" "etiqueta" => "Fig. 10" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr10.jpeg" "Alto" => 753 "Ancho" => 980 "Tamanyo" => 67308 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0050" "detalle" => "Fig. 1" "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0050" class="elsevierStyleSimplePara elsevierViewall">Immunoglobulins synthesis after vaccine injection.</p>" ] ] 10 => array:8 [ "identificador" => "f0055" "etiqueta" => "Fig. 11" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr11.jpeg" "Alto" => 2278 "Ancho" => 2008 "Tamanyo" => 341777 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0055" "detalle" => "Fig. 1" "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0055" class="elsevierStyleSimplePara elsevierViewall">The immune cells in various states. (a) B cell isotypes, (b) T helper cell isotypes, (c) T cytotoxic isotypes, (d) natural killer cell population, (e) macrophage population, and (f) dendritic cells.</p>" ] ] 11 => array:8 [ "identificador" => "f0060" "etiqueta" => "Fig. 12" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr12.jpeg" "Alto" => 709 "Ancho" => 945 "Tamanyo" => 63861 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0060" "detalle" => "Fig. 1" "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0060" class="elsevierStyleSimplePara elsevierViewall">Concentration of cytokines and interleukins induction by the vaccine construct.</p>" ] ] 12 => array:8 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0065" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">CTL</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Allele \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Start \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">End \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Length \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Peptide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Icore \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Score \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-A*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KVESEPKL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KVESEPKL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001432 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-A*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MAHQELGM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MAHQELGM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.000793 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-A*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SEPKLEGR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SEPKLEGR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.000297 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-A*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EEGDKVKV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EEGDKVKV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.000182 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-A*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FEEGDKVK \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FEEGDKVK \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.000156 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-A*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LRFRGREM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LRFRGREM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.000129 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-A*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VESEPKLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VESEPKLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.000108 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-A*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IAKVESEP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IAKVESEP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.5e–05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-A*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VKMKAAQR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VKMKAAQR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4e–05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-A*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">QMMMVLAP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">QMMMVLAP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.2e–05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">HLA-A*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">AKVESEPK \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">AKVESEPK \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">2.5e–05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">HTL</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Allele \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Start \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">End \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Length \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Peptide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Percentile rank</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EMAHQELGMKLLQRV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VTLRFRGREMAHQEL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KVTLRFRGREMAHQE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VKVTLRFRGREMAHQ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PKLEGRQMMMVLAPR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FRGREMAHQELGMKL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EPKLEGRQMMMVLAP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GREMAHQELGMKLLQ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LRFRGREMAHQELGM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">REMAHQELGMKLLQR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RGREMAHQELGMKLL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SEPKLEGRQMMMVLA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KVKVTLRFRGREMAH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RFRGREMAHQELGMK \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DKVKVTLRFRGREMA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GDKVKVTLRFRGREM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EDTVEIAKVESEPKL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EGDKVKVTLRFRGRE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KEDTVEIAKVESEPK \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EEGDKVKVTLRFRGR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DTVEIAKVESEPKLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TVEIAKVESEPKLEG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VEIAKVESEPKLEGR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ESEPKLEGRQMMMVL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FEEGDKVKVTLRFRG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FFEEGDKVKVTLRFR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">QRFFEEGDKVKVTLR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RFFEEGDKVKVTLRF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AAQRFFEEGDKVKVT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KAAQRFFEEGDKVKV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VESEPKLEGRQMMMV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EIAKVESEPKLEGRQ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">84.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IAKVESEPKLEGRQM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">84.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RVKEDTVEIAKVESE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">84.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VKEDTVEIAKVESEP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">QRVKEDTVEIAKVES \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KVESEPKLEGRQMMM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">91.00</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">HLA-DRB1*01:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">AKVESEPKLEGRQMM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">92.00</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">B cell</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">No. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Start \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">End \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Peptide</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Length</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VEIAKVESEPKLEGR</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3530301.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0065" class="elsevierStyleSimplePara elsevierViewall">Lists of predicted T- and B cell epitopes selected as antigenic, non-toxic, and non-allergenic.</p>" ] ] 13 => array:8 [ "identificador" => "t0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0070" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PDB ID \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Binding energies (kcal/mol) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DRB1*0101 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2FSE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DRB3*0202 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1A6A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−11.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-A*11:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5WJL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−9.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HLA-DRB1*04:01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5JLZ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−10.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TLR-8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3W3M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−12.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TLR-3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2A0Z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−8.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3530302.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0070" class="elsevierStyleSimplePara elsevierViewall">Docking affinity result between the vaccine and MHC alleles and TLRs obtained by prodigy server.</p>" ] ] 14 => array:8 [ "identificador" => "t0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0075" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AA \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">length \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Aliphatic \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Aromatic \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-polar \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Polar \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Charged \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Net charge \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hydrophobicity \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Molecular weight \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">897 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">301 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">509 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">388 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">314 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100966.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3530303.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0075" class="elsevierStyleSimplePara elsevierViewall">Vaccine toxicity analysis using CSM program.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:40 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." 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"referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleItalic">Brucella</span> – virulence factors, pathogenesis and treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. Głowacka" 1 => "D. Żakowska" 2 => "K. Naylor" 3 => "M. Niemcewicz" 4 => "A. Bielawska-Drózd" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.21307/pjm-2018-029" "Revista" => array:7 [ "tituloSerie" => "Pol J Microbiol." "fecha" => "2018" "volumen" => "67" "numero" => "2" "paginaInicial" => "151" "paginaFinal" => "161" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30015453" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bb0035" "etiqueta" => "7." 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"referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "DNA immunization as an efficient strategy for vaccination, Avicenna" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Bolhassani" 1 => "S.R. Yazdi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Med Biotechnol." "fecha" => "2009" "volumen" => "1" "numero" => "2" "paginaInicial" => "71" "paginaFinal" => "88" ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack743296" "titulo" => "Acknowledgements" "texto" => "<p id="p0700" class="elsevierStylePara elsevierViewall">Authors would like to thank simlab.uams.edu on providing a free license to use GROMACS simulation package for performing the molecular dynamic simulation.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/15769887/0000002500000002/v2_202405080710/S1576988723000997/v2_202405080710/en/main.assets" "Apartado" => array:4 [ "identificador" => "17855" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Originales" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15769887/0000002500000002/v2_202405080710/S1576988723000997/v2_202405080710/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1576988723000997?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 4 | 8 |
| 2024 October | 14 | 12 | 26 |
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| 2024 May | 20 | 21 | 41 |
| 2024 April | 14 | 13 | 27 |
| 2024 March | 10 | 10 | 20 |
| 2024 February | 10 | 5 | 15 |
| 2024 January | 7 | 0 | 7 |
| 2023 December | 13 | 0 | 13 |
| 2023 November | 5 | 4 | 9 |
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