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The three Southern African Territories &#40;SAT&#41; serotypes were found only in Africa until 1962 and later identified in the Middle East&#46; Serotypes A&#44; O&#44; and C are responsible foroutbreaks in Europe and South America&#46;<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a> Infections with FMDV serotype Asia 1 have occurred in various parts of Asia&#46; Infections with FMDV serotypes O&#44; A&#44; C and ASIA-1 have been reported in India&#46;<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">FMD is highly contagious among cloven-hooved livestock and wildlife&#46; It can spread through contact with contaminated feed&#44; clothing and farming equipment&#46;<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a> Although adult animals generally recover from FMDV infection&#44; the morbidity rate is very high in na&#239;ve populations&#46; FMD is endemic in almost all developing countries causing severe economic loss to both livestock and agriculture trades&#46;<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a> In particular&#44; India is a highly vulnerable developing country owing to its large livestock population&#46; Recent evidence suggests that 2&#44;500 annual outbreaks of FMD occur in India and this leads to a loss of approximately 3&#46;75 millions USD&#46;<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a> The economic impact of these outbreaks are measurable in several ways including significant reduction in milk yield&#44; exporting of animals or animal products&#44; and&#44; of course&#44; animal deaths and spontaneous abortions&#46;<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">Like other viruses&#44; the FMDV continually evolves and mutates&#46; Infection with any one serotype does not confer immunity against another serotype and within serotypes many strains have be identified further diversifying the antigenic profile of the virus&#46; Currently&#44; there is no uniformly effective vaccine available for FMDV although inactivated viral vaccines formulated with adjuvants are commercially available&#46;<a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a> Unfortunately&#44; the existing vaccines do not provide adequate protection&#46;<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a></p><p id="p0020" class="elsevierStylePara elsevierViewall">Protective immune responses to viral infections following initial infection impart immunological memory to the host&#44; involve the activation of antigen-specific B and T lymphocytes&#46; While B cell antibody responses play a critical role&#44; anti-viral CTLs are essential to viral eradication and lifelong immunity&#46;<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a> Generation of protective immune responses to intracellular infections like those caused by FMDV depends upon activation of virus-specific T helper cells which produce cytokines that help manifest cell activation events leading to viral-specific B- and T-cell proliferation&#44; differentiation&#44; and ultimately&#44; memory&#46; In the case of T cell responses&#44; T helper cells are also responsible for cell activation events needed to stimulate viral-specific CTLs&#46; In addition&#44; unlike B cell responses&#44; activation of T helper cells and CTLs require antigen processing and presentation of viral epitopes in the context of major histocompatibility complex &#40;MHC&#41; molecules expressed by so-called antigen-presenting cells &#40;APC&#41;&#46; Specifically&#44; CTL responses require APC presentation of proteosomally cleaved viral epitopes bound to MHC class I molecules&#46; Much of what is known regarding adaptive immune responses has been studied in mouse and human experimental paradigms but it is clear that similar cell players &#40;e&#46;g&#46; B cells&#44; CD4<span class="elsevierStyleHsp" style=""></span>&#43; T helper cells and CD8<span class="elsevierStyleHsp" style=""></span>&#43; CTLs&#41; in cattle and swine&#46;<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a> Thus&#44; adaptive immune responses mediated by T lymphocytes in cattle and swine are also dependent upon MHC molecules expressed by APCs which activate cells expressing epitope-specific T cell receptors&#46; In the case of CD8<span class="elsevierStyleHsp" style=""></span>&#43; T cells which differentiate into virus-specific effector CTLs&#44; APC MHC class I molecules typically bind to viral peptides &#40;epitopes&#41; containing 8-11 amino acids&#46;<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> Epitopes which bind with high affinity can provoke a CD8<span class="elsevierStyleHsp" style=""></span>&#43; immune response&#44; resulting in the destruction of infected cells by CTLs&#46; Hence&#44; in order to develop effective epitope-based FMDV vaccines&#44; a critical starting point involves the identification of CTL epitopes capable of binding MHC class I molecules expressed by APC&#46;<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> Each MHC allele has a characteristic peptide binding preference which can be determined by using various prediction algorithms&#46;<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> Moreover&#44; many computational tools are available for the prediction of T cell epitopes&#46; In this study&#44; we used IEDB-AR and NetMHCpan 2&#46;8 tools for predicting the FMDV epitopes likely to have a strong ability to bind specific MHC class I alleles in a bovine system&#46;<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a></p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Methods</span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Protein sequence retrieval</span><p id="p0025" class="elsevierStylePara elsevierViewall">Three vaccine strains&#44; Asia1 IND63&#47;72&#44; TypeA IND17&#47;82&#44; TypeA IND40&#47;00&#44; which are routinely used in India for the preparation of adjuvant-based inactivated FMDV vaccines were selected for study All three strains have common structural and non-structural proteins&#44;but they differ in their amino acid sequences&#46; Four structural &#40;VP4&#44; VP2&#44; VP3 and VP1&#41; and 7 non-structural &#40;2A&#44; 2B&#44; 2C&#44; 3A&#44; 3B&#44; 3C and 3D&#41; protein sequences of FMDV were retrieved from Virus Pathogen Database and Analysis Resource &#40;ViPR&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> Using the Uniprot database &#40;<a href="http://www.uniprot.org/">http&#58;&#47;&#47;www&#46;uniprot&#46;org&#47;</a>&#41;&#44; we retrieved polyprotein sequences of 17 Indian strains of Asia 1 serotype &#40;A6XP76&#44; A6XP77&#44;A6XP81&#44; A6XP94&#44; A6XP95&#44; A6XP91&#44;Q68IQ3&#44;A6XP82&#44;A6XP87&#44;A6XP83&#44;A6XP79&#44; A6XP80&#44; A6XP93&#44; A6XP96&#44; A6XP88&#44; A6XP92 and A6XP78&#41; and 13 Indian strains of Type A serotype &#40;F6L6S3&#44; F6L6S1&#44; E1APE5&#44; F6L6S2&#44; E1APE7&#44; F6L6R9&#44; F6L6R1&#44; F6L6R6&#44; F6L6S0&#44; F6L6R5&#44; F6L6R2&#44; E1APE6 and F6L6Q7&#41;&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Prediction of CTL epitopes</span><p id="p0030" class="elsevierStylePara elsevierViewall">Prediction of CTL epitopes of the FMDV proteome &#40;2 strains of A serotype and 1 stain of Asia 1 serotype&#41; was done using two tools&#44; namely&#44; Immune Epitope Data Base Analyzing Resource &#40;IEDB-AR&#41;&#40;<a href="http://tools.immuneepitope.org/main/index.html">http&#58;&#47;&#47;tools&#46;immuneepitope&#46;org&#47;main&#47;index&#46;html</a>&#41; and NetMHCpan2&#46;8 &#40;<a href="http://www.cbs.dtu.dk/services/NetMHCpan/">http&#58;&#47;&#47;www&#46;cbs&#46;dtu&#46;dk&#47;services&#47;NetMHCpan&#47;</a>&#41;&#46; Each of the predicted epitopes was individually analyzed using these two programs for the presence of putative 8-&#44; 9-&#44; 10- and 11-mer epitopes that can bind to MHC class I allele BoLA T2b&#46; The IEDB-recommended prediction method was selected as a default for IEDB analysis&#46; Low percentile ranks indicate strong binding to MHC molecules&#46; Therefore&#44; in the present study&#44; peptides with &#8804;<span class="elsevierStyleHsp" style=""></span>1&#37; percentile scores were considered to be potent epitopes by IEDB analysis&#46;<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> The default prediction method was also selected for NetMHCpan 2&#46;8 analysis&#46; The predicted CTLFMDV epitopes were Blasted against the proteome of cattle so as to identify identical sequences expressed in cattle&#46; Any epitopes that were found to be present in both cattle and FMDV were eliminated from further study as candidate epitopes due to their potential for triggering autoimmune responses in an epitope-based vaccine&#46;</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Overlapping epitope prediction</span><p id="p0035" class="elsevierStylePara elsevierViewall">Despite the relatively high performance of IEDB-AR and NetMHCpan 2&#46;8&#44; the approach of predicting CTL epitopes across a large proteome based on just prediction algorithms remains challenging since the efficiency of these tools are not known&#46; Hence&#44; by determining FMDV peptide sequences predicted as CTL epitopes using both tools fortified our confidence regarding the identification of possible immunogenic peptides derived from each viral strain&#46; This was accomplished by manually aligning and comparing predicted T cell epitopes derived from each algorithm in order to identify overlapping epitopes&#46;</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Antigenicity prediction</span><p id="p0040" class="elsevierStylePara elsevierViewall">VaxiJen is a tool for predicting the immunogenicity of protein sequences&#46; The predicted overlapping epitopes were screened for their antigenicity using antigen prediction server VaxiJen v2&#46;0 &#40;<a href="http://www.ddg-pharmfac.net/vaxijen/VaxiJen/VaxiJen.html">http&#58;&#47;&#47;www&#46;ddg-pharmfac&#46;net&#47;vaxijen&#47;VaxiJen&#47;VaxiJen&#46;html</a>&#41;&#46; The default prediction method was selected for analysis&#46;</p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Binding to other alleles</span><p id="p0045" class="elsevierStylePara elsevierViewall">Each MHC class I allele has its own characteristic binding preference based on their intrinsic peptide binding site&#44; amino acid composition and resulting topography&#46; Characterizing peptide-binding of the FMDV proteome to each of these alleles is not feasible&#46; Therefore&#44; all overlapping epitopes were further analyzed for the binding efficiency with other BoLA alleles available for analysis using the NetMHCpan 2&#46;8 and IEDB-AR server&#46; The NetMHCpan 2&#46;8 server provides MHC class I binding prediction for 103 BoLA alleles whereas IEDB-AR provides 87 BoLA alleles for class I binding prediction&#46;</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Multiple sequence alignment</span><p id="p0050" class="elsevierStylePara elsevierViewall">Multiple sequence alignment of overlapping epitopes with polyproteins of 13 Indian strains of type A and 17 Indian strains of Asia 1 serotype helped us determine FMDV consensus epitopes&#46; This was accomplished using the ClustalW2 multiple sequence alignment analysis tool&#46; Theoretically&#44; use of such peptide in epitope-based vaccines would provide protection against a wide range of FMDV strains&#46;</p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Consensus epitope prediction</span><p id="p0055" class="elsevierStylePara elsevierViewall">Comparison of overlapping peptide sequences predicted from proteomes of A IND40&#47;00&#44; A IND 17&#47;82 and Asia-1 IND 63&#47;72 allowed us to further reduce the number of epitopes for further study&#46; Looking forward&#44; such a comparison leading to the identification of consensus epitopes would facilitate the development of multivalent peptide vaccines against Indian strains of 2 serotypes namely&#44; Type A and Asia 1&#46;</p></span></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">BoLA-T2b structure modeling and refinement</span><p id="p0060" class="elsevierStylePara elsevierViewall">The sequence of BoLA-T2b allele &#40;Accession number&#58; Q1JU88&#41; was retrieved from UniProt Database &#40;<a href="https://www.uniprot.org/">https&#58;&#47;&#47;www&#46;uniprot&#46;org&#47;</a>&#41;&#46; Since the crystal structure is not available&#44; the structure of BoLA-T2b was modeled using I-TASSER server &#40;<a href="https://zhanggroup.org/I-TASSER/">https&#58;&#47;&#47;zhanggroup&#46;org&#47;I-TASSER&#47;</a>&#41;&#46; The structural quality of the selected model was refined using 3Drefine server &#40;<a href="http://sysbio.rnet.missouri.edu/3Drefine/">http&#58;&#47;&#47;sysbio&#46;rnet&#46;missouri&#46;edu&#47;3Drefine&#47;</a>&#41;&#46;</p></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Molecular docking</span><p id="p0065" class="elsevierStylePara elsevierViewall">The 3D structures of the predicted antigenic CTL epitopes were modeled using ChemSketch and Discovery Studio Visualizer Software&#46; Molecular docking was performed for predicted antigenic CTL epitopes with BoLA-T2b allele using PyRx&#44; an open-source docking tool&#46; PyRx uses AutoDock Vina module to perform docking&#46; Molecular docking provides information regarding the binding energy and amino acid interaction between the predicted epitopes of FMD with the BoLA-T2b allele&#46;</p></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Results</span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Prediction of CTL epitopes</span><span id="s0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">IEDB-AR analysis</span><p id="p0070" class="elsevierStylePara elsevierViewall">A total of 207 epitopes&#44; restricted by the BoLa T2b allele&#44; were predicted using the IEDB-AR tool &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46; Among these&#44; 72 epitopes were predicted from proteins of the ASIA-1 IND 63&#47;72 proteome&#44; in which26 peptides &#40;36&#46;11 &#37;&#41;were 11-mer&#44;24 &#40;33&#46;33 &#37;&#41;were 8-mers&#44; 15 &#40;20&#46;83 &#37;&#41; were 10-mers&#44; and 7 &#40;9&#46;72 &#37;&#41; were 9-mer in length&#46; In the case of the TypeA IND 17&#47;82 proteome&#44; a total&#44; 67 epitopes were predicted&#46; Among these&#44; 25 &#40;37&#46;31 &#37;&#41;&#44; 21 &#40;31&#46;34 &#37;&#41;&#44; 15 &#40;22&#46;39 &#37;&#41; and 6 &#40;8&#46;96 &#37;&#41; were 11-&#44; 8-&#44; 10- and 9-mer peptides respectively&#46; Sixty-eight epitopes were predicted by Type A IND 40&#47;00 proteome analysis&#44; of which 27 &#40;39&#46;71 &#37;&#41; epitopes were 11-mers&#44; 14 &#40;20&#46;59 &#37;&#41; were 10-mers&#44; 5 &#40;7&#46;35 &#37;&#41; were 9-mers and 22 &#40;32&#46;35 &#37;&#41; were 8-mers&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia></span></span><span id="s0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0105">NetMHCpan 2&#46;8 analysis</span><p id="p0075" class="elsevierStylePara elsevierViewall">A larger number of FMDV epitopes &#40;489 total&#41; were predicted using the NetMHCpan 2&#46;0 tool &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46; Among these&#44; 163 epitopes were predicted in the proteome of ASIA-1 IND 63&#47;72&#44; of which 45 &#40;27&#46;61&#37;&#41; peptides were 11-mers&#44; 44 &#40;26&#46;99&#37;&#41; were 9-mers&#44; 40 &#40;24&#46;54&#37;&#41; were 10-mers&#44; and 34 &#40;20&#46;86&#37;&#41; were 8 mers&#46; A similar number of epitopes &#40;164&#41; were predicted by TypeA IND 17&#47;82 proteome analysis&#46; Forty-four &#40;26&#46;83&#37;&#41;&#44; 41 &#40;25&#37;&#41;&#44; 43 &#40;26&#46;22&#37;&#41; and 36 &#40;21&#46;95&#37;&#41; epitopes were found to be 11-&#44; 10-&#44; 9- and 8-mer peptides&#44; respectively&#46; Finally&#44; analysis of the proteome of Type AIND 40&#47;00&#44; revealed 162 predicted epitopes of which 44 peptides &#40;27&#46;16&#37;&#41; were 11-mers&#44; 44 &#40;27&#46;16&#37;&#41; were 9-mers&#44; 39 &#40;40&#46;07&#37;&#41; were 10-mers and 35 &#40;21&#46;60&#37;&#41; were 8 mers&#46;</p></span><span id="s0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0110">Overlapping epitope prediction</span><p id="p0080" class="elsevierStylePara elsevierViewall">A total of 150 overlapping epitopes were predicted in 2 strains of A serotype and 1 stain of Asia 1 serotype &#40;<a class="elsevierStyleCrossRef" href="#f0005">Fig 1</a>&#41;&#46; By analyzing the proteome of the Asia 1 IND 63&#47;72 strain&#44; 72 peptides were predicted as epitopes using the IEDB-AR tool whereas 163 were predicted using the NetMHCpan tool&#46; A comparison of these two sets of data showed that 52 peptides were predicted as overlapping epitopes&#46; FMDV strains Type A IND 17&#47;82 and Type A IND 40&#47;00 contained 48 and 50 overlapping predicted epitopes&#44; respectively&#46; Each of these overlapping epitopes was then subjected to antigenicity analysis as described below&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia></span><span id="s0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0115">Antigenicity prediction</span><p id="p0085" class="elsevierStylePara elsevierViewall">Using the VaxiJen v2&#46;0 tool&#44; 26 antigenic epitopes were predicted out of 52 overlapping epitopes for the Asia 1 &#40;IND63&#47;72&#41; strain&#59; 23 &#40;out of 48&#41; and 23 &#40;out of 50&#41; antigenic epitopes were predicted in Type A &#40;IND 17&#47;82&#41; and Type A &#40;IND 40&#47;00&#41; strain&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#f0010">Fig 2</a>&#41;&#46;</p><elsevierMultimedia ident="f0010"></elsevierMultimedia></span><span id="s0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0120">Binding to other alleles</span><p id="p0090" class="elsevierStylePara elsevierViewall">The overlapping epitopes were analyzed for their predicted ability to bind binding other BoLA alleles available in IEDB-AR &#40;10 alleles&#41; and NetMHCpan &#40;103 alleles&#41;&#46; The Asia 1 &#40;IND63&#47;72&#41; strain VP 1 protein epitope MQIPSHTL<span class="elsevierStyleInf">53-60</span> binds with 67 out of 103 alleles analyzed in NetMHCpan2&#46;8 tool&#46; Two epitopes&#44; namely VP2&#8211;DQYKLHKPWTL<span class="elsevierStyleInf">169-179</span>&#44; 2C- AMFQYDCALL<span class="elsevierStyleInf">260-269</span> were found to bind with 6 out of 10 alleles using IEDB-AR analysis&#46; Likewise&#44; the predicted epitope&#44; AMFQYDCALL<span class="elsevierStyleInf">260-269</span> present in 2C protein of Type A &#40;IND17&#47;82&#41; and Type A &#40;IND40&#47;00&#41; exhibited higher binding ability with other BoLA alleles in NetMHCpan and IEDB-AR analysis&#46; Results of the Asia 1 &#40;IND63&#47;72&#41;&#44; Type A &#40;IND 17&#47;82&#41; and Type A &#40;IND 40&#47;00&#41; epitopes binding studies are presented in <a class="elsevierStyleCrossRefs" href="#t0010">Tables 2&#44; 3&#44; and 4</a>&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="t0015"></elsevierMultimedia><elsevierMultimedia ident="t0020"></elsevierMultimedia></span><span id="s0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0125">Multiple sequence alignment</span><p id="p0095" class="elsevierStylePara elsevierViewall">Polyprotein sequences of 17 Indian strains of the Asia 1 serotype were retrieved from the Uniprot database and multiple sequences alignment were performed with peptides of Asia 1 IND 63&#47;72&#46;12 Epitopes of IND 63&#47;72 were found in all 17 Indian Strains of Asia I serotype &#40;Supplementary file 1&#41;&#46; Multiple sequence alignment was performed for peptides of Type A IND 17&#47;82 and IND 40&#47;00 strains with polyprotein sequences of 13 Indian strains of Type A serotype&#46; A total of 23 epitopes of IND 17&#47;82were found in all 13 Indian strains of Type A serotype&#40;Supplementary file 2&#41;&#46; Similarly&#44; in aligning the sequence of IND 40&#47;00 with the 13 Indian strains&#44; 24 epitopes were found to have similarity with the polyproteins of 13 Indian strains of Type A&#40;Supplementary file 3&#41;&#46;</p></span><span id="s0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0130">Consensus epitope prediction</span><p id="p0100" class="elsevierStylePara elsevierViewall">The overlapping epitopes predicted for strains Asia1 IND 63&#47;72&#44; Type A IND 17&#47;82 and Type A IND 40&#47;00 were compared to determine consensus epitopes&#46; A total of 29 consensus epitopes were predicted &#40;<a class="elsevierStyleCrossRef" href="#t0025">Table 5</a>&#41;&#46; Among these&#44; 28 epitopes were present to in all strains of A serotype and 1 strain of Asia 1 serotype&#46; The epitope VP3-AQYYAQYSGTI was found to be present in Asia 1 IND 63&#47;72 and Type A IND 17&#47;82 serotypes&#46;</p><elsevierMultimedia ident="t0025"></elsevierMultimedia></span></span><span id="s0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0135">BoLA-T2b structure modeling and refinement</span><p id="p0105" class="elsevierStylePara elsevierViewall">Five models were generated for BoLA-T2b by the I-TASSER server using the threading templates &#40;PDB Hit&#58; 7edoA&#44; 7rtdA&#44; 6ujo&#44; 2bck&#44; 1mhcA&#44; 6apnA&#44; 6ujoA&#44; 7rtdA&#44; 4cvxA and 6lf9D&#41;&#46; The calculated C-score values for models 1 to 5 were -1&#46;43&#44; -2&#46;11&#44; -2&#46;74&#44; -2&#46;07 and -3&#46;03 respectively&#46; Since&#44; higher the C-score there is higher the level of confidence&#44; model 1 with C-score of -1&#46;43 was selected for further studies&#46; This model was further refined by 3Drefine server&#46; This server provided five models with different parameters&#44; including the 3D refined scores&#44; GDT-TS&#44; GDTHA&#44; RMSD&#44; MolProbity and RWPlus&#46; Higher the GDT-TS&#44; GDTHA and RMSD values and lower the RWplus and MolProbity values indicate a higher quality for the models&#46; The refined model 1 was selected based on the above parameters&#46; The results are presented in Supplementary Fig&#46; 1&#46;</p></span><span id="s0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0140">Molecular docking</span><p id="p0110" class="elsevierStylePara elsevierViewall">The predicted CTL epitopes were docked with the modeled BoLA-T2b allele&#46; Three consensus CTL epitopes&#44; <span class="elsevierStyleBold">AQYYAQYSGTI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">95-106</span></span> and <span class="elsevierStyleBold">AEACPTFLCF</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">48-58</span></span> of VP3 protein&#44; consensus to Type A &#40;IND17&#47;82&#41;&#44; Type A &#40;IND40&#47;00&#41;&#44; were the top binders with the lower binding energies of -9&#46;2 kcal&#47;mol and -8&#46;8 kcal&#47;mol respectively&#46; This was followed by <span class="elsevierStyleBold">FQYDCALL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">262-270</span></span> of VP3 consensus to Asia 1 &#40;IND63&#47;72&#41;&#44; Type A &#40;IND17&#47;82&#41;&#44; Type A &#40;IND40&#47;00&#41; with a binding energy of -8&#46;8 kcal&#47;mol &#40;<a class="elsevierStyleCrossRef" href="#f0015">Fig&#46; 3</a>&#41;&#46; Four non-consensus CTL epitopes from VP1&#44; <span class="elsevierStyleBold">AETYCPRPL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">180-189</span></span> and <span class="elsevierStyleBold">AETYCPRPLL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">180-190</span></span> of Asia 1 &#40;IND63&#47;72&#41;&#44; <span class="elsevierStyleBold">AQRRHHTDVSF</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">24-35</span></span> of Type A &#40;IND17&#47;82&#41; and <span class="elsevierStyleBold">GQLAARIAAQL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">148-159</span></span> of Type A &#40;IND40&#47;00&#41; exhibited binding energies of -9&#46;3&#44; -9&#46;1&#44; -8&#46;5 and -9&#46;2 kcal&#47;mol respectively &#40;<a class="elsevierStyleCrossRef" href="#f0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="f0015"></elsevierMultimedia></span><span id="s0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0145">Discussion</span><p id="p0115" class="elsevierStylePara elsevierViewall">Chemical inactivation of FMDV is commonly used to prepare vaccines which are then used together with adjuvants for vaccination of livestock&#46; Unfortunately&#44; these vaccines require regular booster immunizations and their efficacy is low&#46;<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a> In addition&#44; studies have shown that accidental release of the virus has occurred due to incomplete viral inactivation&#46;<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a> Therefore&#44; alternative strategies for producing safe and effective vaccines are being investigated&#46; Chemically synthesized immunogenic epitopes which are derived from immunogenic regions of the virus have been used as a potential vaccine&#44; although protective immune response rates were low&#46;<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a> In general&#44; effective vaccines against intracellular pathogens such as FMDV stimulate B- and T-cell responses provoking both humoral and cell mediated immune responses&#44; respectively&#46; Most of the reported FMDV vaccine studies have focused on the use of B cell epitopes to induce virus-neutralizing antibody responses&#46;<a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a> Two epitopes &#40;VP <span class="elsevierStyleInf">138-154</span> and VP <span class="elsevierStyleInf">200-213</span>&#41; from FMDV are able to provoke neutralizing antibody response against the homologous viral type&#46;<a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a> Broadening the approach for FMDV vaccine development by focusing on strategies aimed at stimulating anti-FMDV CTL responses should be considered in light of the clear protective role played by such effector cells in viral infections&#46;<a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a> As a relatively new experimental paradigm for vaccine development&#44; <span class="elsevierStyleItalic">in silico</span> approaches has shown promise and it has the distinct advantage of eliminating the need to use hazardous live pathogens to identify immunogenic epitopes&#46;</p><p id="p0120" class="elsevierStylePara elsevierViewall">Most previous studies have focused on the development of epitope-based vaccines using peptides found in single FMDV proteins or serotypes&#46; The majority of immuneodominant conformational epitopes have been found to be present in the G-H loop region of FMDV&#8217;s VP1 protein&#46;<a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a> The advantage of identifying consensus peptides&#44; as was done in the current study&#44; is that it predicts MHC class I binding of such peptides that are expressed in multiple strains of different FMDV serotypes&#46; Furthermore&#44; consensus epitopes were determined by comparing the overlapping peptide sequences of three strains of two FMDV serotypes&#46;</p><p id="p0125" class="elsevierStylePara elsevierViewall">Analysis of the proteome of Asia 1 IND 63&#47;72 strain revealed 72 peptide sequences that qualify as CTL epitopes using the IEDB-AR tool as compared with 163 sequences identified using the NetMHCpan tool&#46; A total of 72 peptides were found to be overlapping of which 26 epitopes were predicted to be antigenic&#46; Peptides binding with alleles other than BoLA T2b allele were also investigated&#46; Using IEDB-AR analysis&#44; fifteen epitopes had predicted binding affinity for more than two alleles&#46; In contrast&#44; using the NetMHCpan tool&#44; 38 epitopes had predicted binding affinity for more than 10 alleles&#46; The vaccine strain Asia 1 IND 63&#47;72 was aligned with polyprotein of other Asia 1 Indian strains to determine similarity between the epitopes of analyzing strain and sequence of other Indian strains&#46; The following 12 epitopes of IND 63&#47;72 were found in 17 Indian strains of Asia I serotype VP4&#58; <span class="elsevierStyleBold">SQNQSGNTGSI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">11-21</span></span><span class="elsevierStyleBold">&#44; VP2- NQFNGGCL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">114-121</span></span><span class="elsevierStyleBold">&#44; AERFFKKHL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">58-66</span></span><span class="elsevierStyleBold">&#44; AERFFKKHLF</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">58-67</span></span><span class="elsevierStyleBold">&#44; AEACPTFL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">48-57</span></span><span class="elsevierStyleBold">&#44; AEACPTFLRF</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">48-57</span></span><span class="elsevierStyleBold">&#44; and 2C &#8211; GEWLVKLIL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">16-24</span></span><span class="elsevierStyleBold">&#44; GEWLVKLILAI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">16-26</span></span><span class="elsevierStyleBold">&#44; GQGKSFLANVL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">113-123</span></span><span class="elsevierStyleBold">&#44; DEAEKNPL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">107-114</span></span><span class="elsevierStyleBold">&#44; IEKGQHEAAI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">14-23</span></span><span class="elsevierStyleBold">&#44;</span> and <span class="elsevierStyleBold">DEYRRLFEPF</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">437-446</span></span><span class="elsevierStyleBold">&#46;</span> The number of peptides predicted in the proteome of the Type A IND 17&#47;82 strain by in IEDB-AR&#44; NetMHCpan&#44; overlapping analysis and antigenicity studies were 67&#44; 164&#44; 48 and 23 epitopes&#44; respectively&#46; Eighteen epitopes were found to bind with more than two alleles present using the IEDB-AR tool as compared with 35 that bind with more than 10 alleles using the NetMHCpan 2&#46;8 tool&#46; The following 23 Epitopes of IND 17&#47;82 were found in 13 Indian strains of Type A serotype&#44;VP2&#58; <span class="elsevierStyleBold">NQFNGGCL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">114-121</span></span><span class="elsevierStyleBold">&#44; EETTLLEDRIL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">5-15</span></span><span class="elsevierStyleBold">&#44; 2C - SEEKFVTM</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">36-43</span></span><span class="elsevierStyleBold">&#44; FQYDCALL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">262-269</span></span><span class="elsevierStyleBold">&#44; GEWLVKLIL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">16-24</span></span><span class="elsevierStyleBold">&#44;EEKFVTMTDL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">37-46</span></span><span class="elsevierStyleBold">&#44; AMFQYDCALL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">260-269</span></span><span class="elsevierStyleBold">&#44; AQMVSTTGFI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">175-184</span></span><span class="elsevierStyleBold">&#44; SEEKFVTMTDL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">36-46</span></span><span class="elsevierStyleBold">&#44; EEKFVTMTDLV</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">37-47</span></span><span class="elsevierStyleBold">&#44; GEWLVKLILAI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">16-26</span></span><span class="elsevierStyleBold">&#44; GQGKSFLANVL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">113-123</span></span><span class="elsevierStyleBold">&#44; 3A - IEKGQHEAAI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">14-23</span></span><span class="elsevierStyleBold">&#44; FEIVALCLTL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">59-68</span></span><span class="elsevierStyleBold">&#44; 3D - PEFGPAAL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">32-39</span></span><span class="elsevierStyleBold">&#44; AEWILKTL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">271-278</span></span><span class="elsevierStyleBold">&#44; DEYRRLFEPF</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">437-446</span></span><span class="elsevierStyleBold">&#44; QEKLISVAGL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">421-430</span></span><span class="elsevierStyleBold">&#44; MEKVRAGKTRI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">170-180</span></span><span class="elsevierStyleBold">&#44; FEALKPHFKSL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">350-360</span></span><span class="elsevierStyleBold">&#44; REYKFACQTFL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">153-163</span></span><span class="elsevierStyleBold">&#44; FEIPSYRSLYL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">450-460</span></span>and <span class="elsevierStyleBold">GLFEIPSYRSL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">448-458</span></span>&#46; Similarly&#44; when the proteome of the Type A IND 40&#47;00 strain was analysed&#44; the number of sequences predicted in IEDB-AR&#44; NetMHCpan&#44; overlapping analysis and antigenicity studies were 68&#44; 162&#44; 50 and 23 epitopes&#44; respectively&#46; Prediction analysis showed that seventeen epitopes were found to bind with more than two alleles using the IEDB-AR tool and 37 epitopes binds with more than 10 alleles using NetMHCpan 2&#46;8 tool&#46; The following 24 epitopes of IND 17&#47;82 were found in 13 Indian strains of Type A serotype&#44; VP2&#58; <span class="elsevierStyleBold">NQFNGGCL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">114-121</span></span><span class="elsevierStyleBold">&#44; EETTLLEDRIL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">5-15</span></span><span class="elsevierStyleBold">&#44; 2C &#8211; SEEKFVTM</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">36-43</span></span><span class="elsevierStyleBold">&#44; FQYDCALL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">262-269</span></span><span class="elsevierStyleBold">&#44; GEWLVKLIL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">16-24</span></span><span class="elsevierStyleBold">&#44; EEKFVTMTDL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">37-46</span></span><span class="elsevierStyleBold">&#44; AMFQYDCALL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">260-269</span></span><span class="elsevierStyleBold">&#44; AQMVSTTGFI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">175-184</span></span><span class="elsevierStyleBold">&#44; SEEKFVTMTDL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">36-46</span></span><span class="elsevierStyleBold">&#44; EEKFVTMTDLV</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">37-47</span></span><span class="elsevierStyleBold">&#44; GEWLVKLILAI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">16-26</span></span><span class="elsevierStyleBold">&#44; GQGKSFLANVL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">113-123</span></span><span class="elsevierStyleBold">&#44; 3A &#8211; FEIVALCL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">59-66</span></span><span class="elsevierStyleBold">&#44; IEKGQHEAAI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">14-23</span></span><span class="elsevierStyleBold">&#44; FEIVALCLTL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">59-68</span></span><span class="elsevierStyleBold">&#44; 3D &#8211; PEFGPAAL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">32-39</span></span><span class="elsevierStyleBold">&#44; AEWILKTL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">271-278</span></span><span class="elsevierStyleBold">&#44; DEYRRLFEPF</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">437-446</span></span><span class="elsevierStyleBold">&#44; QEKLISVAGL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">421-430</span></span><span class="elsevierStyleBold">&#44; MEKVRAGKTRI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">170-180</span></span><span class="elsevierStyleBold">&#44; FEALKPHFKSL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">350-360</span></span><span class="elsevierStyleBold">&#44; REYKFACQTFL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">153-163</span></span><span class="elsevierStyleBold">&#44; FEIPSYRSLYL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">450-460</span></span> and <span class="elsevierStyleBold">GLFEIPSYRSL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">448-458</span></span>&#46; Comparing the overlapping sequence of all the 3 strains&#44; 29 consensus epitopes were predicted&#46; All the epitopes predicted from the 3 proteomes were Blasted against the cattle proteome for similarity&#44; but none were found to share 100&#37; identity with the cattle proteome&#46;</p><p id="p0130" class="elsevierStylePara elsevierViewall">The putative epitopes were validated using molecular docking against the BoLA-T2b allele&#46; The predicted epitopes&#44; <span class="elsevierStyleBold">AQYYAQYSGTI</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">95-106</span></span> and <span class="elsevierStyleBold">AEACPTFLCF</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">48-58</span></span> of VP3&#44; consensus to Type A &#40;IND17&#47;82&#41;&#44; Type A &#40;IND40&#47;00&#41;&#44; <span class="elsevierStyleBold">FQYDCALL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">262-270</span></span> of VP3 consensus to Asia 1 &#40;IND63&#47;72&#41;&#44; Type A &#40;IND17&#47;82&#41;&#44; Type A &#40;IND40&#47;00&#41;&#44; <span class="elsevierStyleBold">AETYCPRPL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">180-189</span></span> and <span class="elsevierStyleBold">AETYCPRPLL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">180-190</span></span> of Asia 1 &#40;IND63&#47;72&#41;&#44; <span class="elsevierStyleBold">AQRRHHTDVSF</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">24-35</span></span> of Type A &#40;IND17&#47;82&#41; and <span class="elsevierStyleBold">GQLAARIAAQL</span><span class="elsevierStyleInf"><span class="elsevierStyleBold">148-159</span></span> of Type A &#40;IND40&#47;00&#41; of VP1 protein were binding to the BoLA-T2b with higher binding affinity&#46; Their binding energies were between -8&#46;8 to -9&#46;2 kal&#47;mol &#40;<a class="elsevierStyleCrossRef" href="#f0015">Fig&#46; 3</a>&#41;&#46; This further confirms that the predicted epitopes could be potential epitopes&#46;</p><p id="p0135" class="elsevierStylePara elsevierViewall">The FMDV CTL epitopes predicted in the present study have&#44; to our knowledge&#44; never before been reported&#46; Given the proven utility of epitope prediction methods to identify peptide sequences that qualify as candidates for vaccine development&#44; future studies using synthetically produced FMDV peptides identified in this study will be needed to conform their ability to generate CTL responses and&#44; hopefully&#44; stimulate protective immune responses against this pathogen in hosts predisposed to FMD&#46; Further analysis using <span class="elsevierStyleItalic">in vitro</span> MHC-peptide binding assays and in vivo assays such as CTL assays&#44; IFN-&#947; ELISpot assay and intracellular cytokine staining could confirm the ability of the predicted epitopes to induce specific immune responses&#46;</p></span><span id="s0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0150">Conclusion</span><p id="p0140" class="elsevierStylePara elsevierViewall">Analysis of the proteome of three vaccine strains of FMDV predicted 29 consensus epitopes that can be used as an epitope-based CTL-inducing vaccine candidate for both Asia I&#44; Type A serotypes&#46; Further confirmation in determining the efficacy of this approach needs to be explored using well-established <span class="elsevierStyleItalic">in vitro</span> and <span class="elsevierStyleItalic">in vivo</span> approaches in the future&#46;</p></span></span>"
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          "titulo" => "Introduction"
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              "titulo" => "Protein sequence retrieval"
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              "titulo" => "Binding to other alleles"
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              "titulo" => "Multiple sequence alignment"
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              "titulo" => "Consensus epitope prediction"
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          "titulo" => "BoLA-T2b structure modeling and refinement"
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              "titulo" => "Prediction of CTL epitopes"
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              "titulo" => "NetMHCpan 2&#46;8 analysis"
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              "titulo" => "Overlapping epitope prediction"
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              "titulo" => "Consensus epitope prediction"
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          "titulo" => "BoLA-T2b structure modeling and refinement"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2021-06-14"
    "fechaAceptado" => "2022-01-21"
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1609755"
          "palabras" => array:5 [
            0 => "Foot and Mouth Disease virus"
            1 => "Epitope"
            2 => "Vaccine"
            3 => "Bola-T2b allele"
            4 => "Cytotoxic T lymphocyte"
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:5 [
            0 => "Virus de la enfermedad boca mano pie"
            1 => "Ep&#237;tope"
            2 => "Vacuna"
            3 => "Alelo Bola-T2b"
            4 => "Linfocitos T citot&#243;xicos"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Objective</span><p id="sp0045" class="elsevierStyleSimplePara elsevierViewall">Foot and Mouth Disease virus &#40;FMDV&#41; commonly affects cloven hoofed animals&#46; Infection with one serotype does not confer immunity to others and currently available vaccines do not provide effective T-cell immunity&#46; The objective of this work is to predict the Cytotoxic T lymphocyte &#40;CTL&#41; epitopes which could be used as vaccine components against FMD virus&#46;</p></span> <span id="as0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Material and methods</span><p id="sp0050" class="elsevierStyleSimplePara elsevierViewall">Proteomes of three Indian FMDV vaccine strains&#44; Type A IND40&#47;00&#44; Type A IND17&#47;82 and Asia-1 IND63&#47;72 were retrieved&#46; BoLa-T2b allele restricted CTL epitopes were predicted using Immune Epitope Data Base Analysis Resource &#40;IEDB-AR&#41; and NetMHCpan 2&#46;8 tool&#46; The predicted overlapping epitopes were further analysed for antigenicity prediction&#44; binding to other BoLA allele and consensus epitope analysis&#46;</p></span> <span id="as0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Results</span><p id="sp0055" class="elsevierStyleSimplePara elsevierViewall">A total of 207 epitopes were predicted by IEDB-AR tool&#46; Among this&#44; 72&#44; 68&#44; 67&#44; epitopes were predicted in Asia 1 IND 63&#47;72&#44; Type A IND40&#47;00 and Type A IND17&#47;82 respectively&#46; Totally 489 epitopes were predicted by NetMHCpan 2&#46;0 tool&#46; Of which&#44; 164&#44; 163 and 162 epitopes were predicted in Type A IND17&#47;82&#44; Asia 1 IND63&#47;72 and Type A IND40&#47;00 respectively&#46; In total 29 consensus epitopes were predicted during this analysis&#44; among this&#44; 28 epitopes are present to occur in all the three Indian strains that were tested&#46;</p></span> <span id="as0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Conclusions</span><p id="sp0060" class="elsevierStyleSimplePara elsevierViewall">The 29 consensus epitopes predicted in this study could be used for developing a potent vaccine for both Asia I and Type A strains of FMD&#46; Further <span class="elsevierStyleItalic">in vitro</span> and <span class="elsevierStyleItalic">in vivo</span> studies are needed to confirm the CTL efficacy of this peptide against FMDV&#46;</p></span>"
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            "identificador" => "as0005"
            "titulo" => "Objective"
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          1 => array:2 [
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            "titulo" => "Material and methods"
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          2 => array:2 [
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        "titulo" => "Resumen"
        "resumen" => "<span id="as10005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st10010">Objetivo</span><p id="sp10045" class="elsevierStyleSimplePara elsevierViewall">El virus boca mano pie &#40;FMDV&#41; afecta de manera com&#250;n a animales ungulados&#46; La infecci&#243;n por un serotipo no confiere la inmunidad al resto&#44; no aportando las vacunas actualmente disponibles inmunidad efectiva a las c&#233;lulas T&#46; El objetivo de este estudio es predecir los ep&#237;topes de los linfocitos T citot&#243;xicos &#40;CTL&#41; que podr&#237;an utilizarse como componentes de la vacuna frente al virus FMD&#46;</p></span> <span id="as30005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st30010">Material y m&#233;todos</span><p id="sp30045" class="elsevierStyleSimplePara elsevierViewall">Se extrajeron los proteomas de tres cepas de vacunas FMDV procedentes de India&#58; IND40&#47;00 Tipo A&#44; IND17&#47;82 Tipo A e IND63&#47;72 Asia-1&#46; Los ep&#237;topes de los CTL restringidos del alelo BoLa-T2b fueron predichos utilizando IEDB-AR &#40;Immune Epitope Data Base Analysis Resource&#41; y la herramienta NetMHCpan 2&#46;8&#46; Los ep&#237;topes superpuestos predichos fueron analizados seguidamente para predecir la antigenicidad&#44; unidos a otros alelos BoLA y ep&#237;topes de consenso&#46;</p></span> <span id="as20005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st20010">Resultados</span><p id="sp20045" class="elsevierStyleSimplePara elsevierViewall">Un total de 207 ep&#237;topes fueron predichos por la herramienta IEDB-AR&#46; Entre ellos&#44; los ep&#237;topes 72&#44; 68 y 67 fueron predichos en IND 63&#47;72 Asia 1&#44; IND40&#47;00 Tipo A e IND17&#47;82 Tipo A&#44; respectivamente&#46; En total&#44; 489 ep&#237;topes fueron predichos por la herramienta NetMHCpan 2&#46;0&#44; de los cuales los ep&#237;topes 164&#44; 163 y 162 fueron predichos en IND17&#47;82 Tipo A&#44; IND63&#47;72 Asia-1 e IND40&#47;00 Tipo A&#44; respectivamente&#46; En total se predijo un total de 29 ep&#237;topes de consenso durante este an&#225;lisis&#44; de los cuales 28 ep&#237;topes est&#225;n presentes en las tres cepas indias que probamos&#46;</p></span> <span id="as80005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st60010">Conclusiones</span><p id="sp80045" class="elsevierStyleSimplePara elsevierViewall">Los 29 ep&#237;topes de consenso predichos en este estudio podr&#237;an utilizarse para desarrollar una vacuna potente para ambas cepas Asia I y Tipo A del FMD&#46; Son necesarios estudios in vitro e in vivo adicionales para confirmar la eficacia de los CTL de este p&#233;ptido frente al FMDV&#46;</p></span>"
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            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
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          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Overlapping epitopes predicted by IEDB-AR and NetMHCpan 2&#46;8 tools&#46; Maximum number of overlapping epitopes were predicted in Asia 1 IND 63&#47;72 strain</p>"
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          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Antigenicity analysis using VaxiJen tool&#46; Maximum number of antigenic epitopes were predicted in Asia 1 &#40;IND 63&#47;72&#41; stain</p>"
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          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0015"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Top binding consensus peptides predicted from Asia 1 &#40;IND63&#47;72&#41;&#44; Type A &#40;IND17&#47;82&#41; and Type A &#40;IND40&#47;00&#41; serotypes&#46; 2D ligand interaction and molecular interaction of predicted CTL epitopes AQYYAQYSGTI &#40;A&#44;B&#41; and AEACPTFLCF &#40;C&#44;D&#41; with BoLA-T2b&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "t0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0020"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PROTEIN</th><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TYPE IND ASIA 1</th><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TYPE IND A 17&#47;82</th><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TYPE IND A 40&#47;00</th></tr><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">IEDB-AR&nbsp;\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">NetMHCpan 2&#46;8&nbsp;\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">IEDB-AR&nbsp;\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">NetMHCpan 2&#46;8&nbsp;\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">IEDB-AR&nbsp;\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">NetMHCpan 2&#46;8&nbsp;\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">L PROTEIN&nbsp;\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&nbsp;\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&nbsp;\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">3&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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">VP4&nbsp;\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">3&nbsp;\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&nbsp;\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">3&nbsp;\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&nbsp;\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">3&nbsp;\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&nbsp;\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">VP3&nbsp;\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">3&nbsp;\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&nbsp;\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">3&nbsp;\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&nbsp;\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">3&nbsp;\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&nbsp;\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">VP2&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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">6&nbsp;\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&nbsp;\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">VP1&nbsp;\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">6&nbsp;\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&nbsp;\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">6&nbsp;\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&nbsp;\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">6&nbsp;\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&nbsp;\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">2A&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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">2B&nbsp;\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">2&nbsp;\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">3&nbsp;\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">2&nbsp;\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">3&nbsp;\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">2&nbsp;\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">3&nbsp;\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">2C&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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">3A&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">8&nbsp;\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&nbsp;\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
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                  \t\t\t\t">3B&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">39&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">40&nbsp;\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
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                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
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                  \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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Peptide predicted for IEDB-AR and NetMHCpan 2&#46;8 tools&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "t0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0025"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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
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                  \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">PROTEIN&nbsp;\t\t\t\t\t\t\n
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                  \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">Start Position&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Length&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Overlapping Peptide&nbsp;\t\t\t\t\t\t\n
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                  \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">NetMHCpan&#40;103&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IEDB&#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">L PROTEIN&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">REIKARLL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">122&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">SEVCMVDGTDM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">1&nbsp;\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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">190&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \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
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                  \t\t\t\t"><span class="elsevierStyleBold">VP4</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">QQYQNSMDTQL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">4&nbsp;\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
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">SQNQSGNTGSI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Analysis of Asia 1 &#40;IND63&#47;72&#41; peptide binding with other BoLA alleles&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "t0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0030"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t">VP1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ELYCPRPL&nbsp;\t\t\t\t\t\t\n
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                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Analysis of Type A &#40;IND17&#47;82&#41; peptide binding with other BoLA alleles&#46;</p>"
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      6 => array:8 [
        "identificador" => "t0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0035"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
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            0 => array:1 [
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                0 => """
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                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">42&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">EETTLLEDRIL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VP3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">48&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">AEACPTFL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">48&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">AEACPTFLCF&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">95&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">AQYYAQYSGTI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">43&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VP1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">MQTHQHGL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">421&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \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">GLFEIPSYRSL&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">Analysis of Type A &#40;IND40&#47;00&#41; peptide binding with other BoLA alleles&#46;</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "t0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0040"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Protein&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Start Position&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Length&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Consensus peptides&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Strains&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">L PROTEIN&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\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
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                  \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_rowgroup " rowspan="8" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Asia 1 &#40;IND63&#47;72&#41;&#44; Type A &#40;IND17&#47;82&#41;&#44; Type A &#40;IND40&#47;00&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">VP4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">QQYQNSMDTQL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">11&nbsp;\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
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                  \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">VP2&nbsp;\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="center" valign="\n
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                  \t\t\t\t">114&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">11&nbsp;\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
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                  \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">VP3&nbsp;\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="center" valign="\n
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                  \t\t\t\t">48&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">AEACPTFL&nbsp;\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
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">AEACPTFLCF&nbsp;\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
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\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">AQYYAQYSGTI&nbsp;\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">Type A &#40;IND17&#47;82&#41;&#44; Type A &#40;IND40&#47;00&#41;&nbsp;\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">2C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">36&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">8&nbsp;\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">SEEKFVTM&nbsp;\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_rowgroup " rowspan="14" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Asia 1 &#40;IND63&#47;72&#41;&#44; Type A &#40;IND17&#47;82&#41;&#44; Type A &#40;IND40&#47;00&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">262&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">FQYDCALL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">GEWLVKLIL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">260&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">AMFQYDCALL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">GEWLVKLILAI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">113&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">GQGKSFLANVL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">3A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">IEFFEGMV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">91&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">NEYIEKANI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">IEKGQHEAAI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">AEKYDKIM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">50&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">EKYDKIML&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
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