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array:23 [ "pii" => "S244514602300002X" "issn" => "24451460" "doi" => "10.1016/j.vacune.2023.01.002" "estado" => "S300" "fechaPublicacion" => "2023-01-01" "aid" => "2352" "copyrightAnyo" => "2023" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Vacunas. 2023;24:68-73" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S1576988722001844" "issn" => "15769887" "doi" => "10.1016/j.vacun.2022.10.002" "estado" => "S300" "fechaPublicacion" => "2023-01-01" "aid" => "264" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Vacunas. 2023;24:68-73" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Estrategia vacunal</span>" "titulo" => "Nirsevimab: hacia la inmunización universal de la población infantil frente al virus respiratorio sincitial" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "68" "paginaFinal" => "73" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Nirsevimab: Towards universal child immunization against respiratory syncytial virus" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1335 "Ancho" => 1722 "Tamanyo" => 166461 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Figura " "rol" => "short" ] ] "descripcion" => array:1 [ "es" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Esquema del procesado de las IgG a través de su unión al receptor FcRn situado en la superficie celular (modificado de Roopenian et al.<a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a>).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Jordi Reina, Carla Iglesias" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Jordi" "apellidos" => "Reina" ] 1 => array:2 [ "nombre" => "Carla" "apellidos" => "Iglesias" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S244514602300002X" "doi" => "10.1016/j.vacune.2023.01.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S244514602300002X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1576988722001844?idApp=UINPBA00004N" "url" => "/15769887/0000002400000001/v1_202302071736/S1576988722001844/v1_202302071736/es/main.assets" ] ] "itemSiguiente" => array:18 [ "pii" => "S2445146023000092" "issn" => "24451460" "doi" => "10.1016/j.vacune.2023.02.006" "estado" => "S300" "fechaPublicacion" => "2023-01-01" "aid" => "260" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Vacunas. 2023;24:74-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:9 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Director</span>" "titulo" => "Vaccine hesitancy and the challenge of controlling COVID-19 and other vaccine-preventable diseases" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "74" "paginaFinal" => "75" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Paulo Ricardo Martins-Filho" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Paulo Ricardo" "apellidos" => "Martins-Filho" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2445146023000092?idApp=UINPBA00004N" "url" => "/24451460/0000002400000001/v1_202302281528/S2445146023000092/v1_202302281528/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S2445146023000080" "issn" => "24451460" "doi" => "10.1016/j.vacune.2023.02.005" "estado" => "S300" "fechaPublicacion" => "2023-01-01" "aid" => "269" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Vacunas. 2023;24:60-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "Vaccination strategies to combat nosocomial infections" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "60" "paginaFinal" => "67" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1986 "Ancho" => 2479 "Tamanyo" => 389307 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Flowchart showing the CDC list of Nosocomial Infections.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rajesh Venkataraman, Umesh Yadav, Ravi Kurikempannadoddi Shivalingegowda, Yogendra Shrestha" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Rajesh" "apellidos" => "Venkataraman" ] 1 => array:2 [ "nombre" => "Umesh" "apellidos" => "Yadav" ] 2 => array:2 [ "nombre" => "Ravi Kurikempannadoddi" "apellidos" => "Shivalingegowda" ] 3 => array:2 [ "nombre" => "Yogendra" "apellidos" => "Shrestha" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2445146023000080?idApp=UINPBA00004N" "url" => "/24451460/0000002400000001/v1_202302281528/S2445146023000080/v1_202302281528/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Vaccine strategies</span>" "titulo" => "Nirsevimab: Towards universal child immunization against respiratory syncytial virus" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "68" "paginaFinal" => "73" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Jordi Reina, Carla Iglesias" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Jordi" "apellidos" => "Reina" "email" => array:1 [ 0 => "jorge.reina@ssib.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cr0005" ] ] ] 1 => array:2 [ "nombre" => "Carla" "apellidos" => "Iglesias" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Virología, Servicio de Microbiología. Hospital Universitario Son Espases, Palma de Mallorca, Spain" "identificador" => "af0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cr0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Nirsevimab: hacia la inmunización universal de la población infantil frente al virus respiratorio sincitial" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 995 "Ancho" => 1575 "Tamanyo" => 87054 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Mutations introduced in the CH2 part of the heavy chain of the Fc fragment to increase affinity for the FcRn receptor and extend the half-life of monoclonal antibodies (modified from Robbie et al.<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a>).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Respiratory syncytial virus (RSV) was discovered in 1955, termed <span class="elsevierStyleItalic">chimpanzee coryza agent</span> and associated with bronchiolitis in children in 1957.<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> It is the cause of acute respiratory illnesses (bronchiolitis and pneumonia) and occurs primarily in epidemic form in the winter months. Although it can affect the entire population, its pathological impact is much greater in children (< 5 years) and the elderly (> 65 years). It is therefore estimated to be responsible for 22% of acute respiratory infections in the paediatric population. A 2015 global study estimated that RSV caused 33.1 million acute respiratory infections per year, resulting in about 3.2 million hospitalisations and about 59,000 hospital deaths in children under 5 years of age.<a class="elsevierStyleCrossRefs" href="#bb0010"><span class="elsevierStyleSup">2–4</span></a> Furthermore, RSV causes about 1.4 million hospitalisations and about 27,300 deaths annually in children under 6 months of age.<a class="elsevierStyleCrossRefs" href="#bb0010"><span class="elsevierStyleSup">2–4</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">After many years of research, there is still no vaccine that has been shown to be effective against RSV. Mainly because the highest rate of hospitalisation occurs in infants under 2 months of age, when the ability to induce an immune response is compromised by the presence of maternal antibodies and the infant immune system is still immature. An alternative to prevent RSV infection or disease is passive immunoprophylaxis using virus-neutralising antibodies.<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1–3</span></a></p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Characteristics of respiratory syncytial virus</span><p id="p0015" class="elsevierStylePara elsevierViewall">RSV is an enveloped virus that has a non-segmented negative single-stranded RNA genome (15,200 nucleotides) containing 10 genes and encoding 11 distinct proteins; it belongs to the family <span class="elsevierStyleItalic">Pneumoviridae</span> and the genus <span class="elsevierStyleItalic">Orthopneumovirus</span>. Four proteins are found in the virus envelope: the matrix protein (M), the small hydrophobic protein (SH), and two glycoproteins labelled F (fusion) and G (attachment glycoprotein)<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> (<a class="elsevierStyleCrossRef" href="#f0005">Fig. 1</a>).</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0020" class="elsevierStylePara elsevierViewall">Glycoproteins F and G are directly involved in the process of infectivity and development of respiratory disease. Thus glycoprotein G is responsible for binding the virus to the epithelial cell, while F is involved in the entry of the virus into the cell, through its fusion with the cytoplasmic membrane; this protein is also responsible for the fusion of the infected cells, leading to the formation of the syncytia, typical of this infection, and which give the virus its name.<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a></p><p id="p0025" class="elsevierStylePara elsevierViewall">Most monoclonal antibodies against RSV use the F glycoprotein as the antigenic element; however, there are two presentations of this F: pre-fusion, inactive trimeric precursor F<span class="elsevierStyleInf">0</span>, (pre-F) and post-fusion (post-F) formed by the F<span class="elsevierStyleInf">1</span> y F<span class="elsevierStyleInf">2</span> subunit after enzymatic hydrolysis. In the pre-F form, an antigenic site called “site zero (Φ)” has been described, which seems to have the highest neutralising antibody-inducing power.<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a> In addition, the post-F form induces a lower immune response, especially in neutralising antibodies.<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a></p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Humanised monoclonal antibodies</span><p id="p0030" class="elsevierStylePara elsevierViewall">The first monoclonal antibodies against the RSV F protein (HNK20, SB209763 and MEDI-493/palivizumab) appeared in the 1990s.<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a> HNK20 was an IgA produced by fusing myeloma cells with lung lymphocytes from immunised mice. Initial studies of intranasal administration in mice and primates showed promising results in protecting against RSV in upper and lower respiratory tract infections.<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a> However, after genetic humanisation, the monoclonal antibody lost its activity both in vitro and in vivo in animal studies, and therefore its use was discontinued.<a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a> The monoclonal antibody SB209763 (also called RSHZ19) was an IgG1. After good results in mice and healthy volunteers, it did not show sufficient clinical efficacy in children at severe risk of RSV infection when compared to MEDI-493. Therefore, in 2002 the FDA approved the monoclonal MEDI-93 (palivizumab) for children at risk for RSV.<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a></p><p id="p0035" class="elsevierStylePara elsevierViewall">Palivizumab (MEDI-493) is a humanised monoclonal antibody against neutralising epitopes located on the pre- and post-fusion forms of the F protein. This antibody is effective in preventing RSV hospitalisations in children at high risk of severe disease (premature infants, chronic lung disease, pulmonary, or cardiac malformations).<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a> This antibody is administered at a dose of 15 mg/kg intramuscularly once a month during the 5-month annual RSV epidemic. However, the high cost of this antibody and the need to administer it monthly renders its use for prophylaxis or immunisation of the entire infant population unfeasible.<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a></p><p id="p0040" class="elsevierStylePara elsevierViewall">Since palivizumab was first used more than 20 years ago, new techniques have been developed to obtain humanised monoclonal antibodies and the main epitopes of the pre-fusion form of the F protein (pre-F) have been characterised, giving them greater neutralising capacity. Genetic modifications have also made it possible to extend the half-life of these antibodies beyond the current 30 days.<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a></p><p id="p0045" class="elsevierStylePara elsevierViewall">Studies by Roopeninan et al.<a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a> and Simister et al.<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> identified the major histocompatibility antigen class I (HLA-I) associated with the neonatal Fc receptor (FcRn) of the constant part of immunoglobulins as an essential element in maintaining and increasing the half-life of IgGs and albumin. The FcRn receptor was originally identified in the process of maternal antibody transport across the placenta and in mouse intestinal cells.<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> In adults, this receptor is located on vascular endothelium and monocytes and is an essential component in the processing of IgG by endocytosis and subsequent intracellular destruction by proteases.<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRefs" href="#bb0090"><span class="elsevierStyleSup">18–20</span></a> One of the characteristics of IgG-FcRn processing is that it is highly pH-dependent. Thus IgG binding to the receptor occurs at acidic pH (6.0) inside the lysosome, while its unbinding occurs at neutral pH (7.4) in the extracellular space.<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a> The increased binding affinity of the Fc region (CH2) of IgG to the FcRn receptor at pH 6, but not at pH 7.4, leads to and ensures efficient recycling of IgG, resulting in the prolongation of its half-life<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> (<a class="elsevierStyleCrossRef" href="#f0010">Fig. 2</a>).</p><elsevierMultimedia ident="f0010"></elsevierMultimedia><p id="p0050" class="elsevierStylePara elsevierViewall">Motavizumab and palivizumab are 2 humanised monoclonal antibodies that act against the pre-F form of RSV by blocking cell binding and attachment, and thus viral infection and replication. Motavizumab has a half-life of about 24 days in the paediatric population (similar to palivizumab). Genetically introduced mutations in 3 amino acids (M252Y/S254T/T256E or YTE) in the CH2 region of the motavizumab heavy chain (mota-YTE), leads to a 10-fold increase in binding to the FcRn receptor in both primates and humans and thus a > 4-fold increase in half-life in vivo.<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> (<a class="elsevierStyleCrossRef" href="#f0015">Fig. 3</a>) This effect is independent of the dose administered (0.3–30 mg/kg), indicating non-saturation of the FcRn system.<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a> The higher affinity and intensity of binding to FcRn means that the monoclonal is not destroyed by the protein (it protects it from lysosomal proteases) and is recycled to the extracellular space, extending the time it is present in the plasma. Furthermore, it has been observed that these mutations do not lead to the formation of anti-monoclonal antibodies, indicating that they are no more immunogenic than the unmodified monoclonal antibody.<a class="elsevierStyleCrossRefs" href="#bb0070"><span class="elsevierStyleSup">14–21</span></a></p><elsevierMultimedia ident="f0015"></elsevierMultimedia></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Nirsevimab</span><p id="p0055" class="elsevierStylePara elsevierViewall">Zhu et al.<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> described in 2017 the compound MEDI8897 which is a humanised kappa monoclonal antibody (recombinant IgG1) that binds to a highly conserved epitope (antigenic site Ø) present in the pre-F form of RSV A and B and exhibits 50-fold higher potency and activity in vitro against RSV compared to palivizumab. In this antibody, the Fc region was genetically modified (YTE mutation in the CH2 heavy chain) to increase its half-life and improve its pharmacokinetics (<a class="elsevierStyleCrossRef" href="#f0015">Fig. 3</a>).</p><p id="p0060" class="elsevierStylePara elsevierViewall">One of the first clinical trials with the monoclonal antibody MEDI8897 was conducted in an adult population to analyse the safety, tolerability and pharmacokinetics of MEDI8897. In a phase 1 placebo-controlled study Griffin et al.<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a> analysed 136 healthy adults who were randomised to receive a single dose of the monoclonal antibody (102 persons) or placebo (34 persons) in 3 branches with intravenous administration (300, 1000, and 3000 mg) and 2 with intramuscular administration (100 mg or 300 mg). The half-life of the monoclonal antibody was 85–117 days in both groups and the bioavailability after the 300 mg dose was 77%; maximum concentration was obtained between days 5 and 9. The presence of anti-monoclonal antibodies was very similar between the monoclonal antibody group (13.7%) and the placebo group (15.2%). The safety profiles were very similar with no significant adverse effects induced by the monoclonal antibody or the antibodies generated against it. This study in adults allows us to establish the main biological parameters of MEDI8897 and the possibility of analysing them in the paediatric population, preferably in preterm infants.<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a></p><p id="p0065" class="elsevierStylePara elsevierViewall">Domachowske et al.<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a> conducted a phase 1b/2a clinical trial studying the optimal dose of the monoclonal antibody MEDI8897 (10, 25, or 50 mg) versus placebo in preterm infants with gestational ages between 32–35 weeks. Analyses of safety, pharmacokinetics, RSV neutralising antibody levels, and anti-drug antibody development were conducted over a 360-day follow-up period.</p><p id="p0070" class="elsevierStylePara elsevierViewall">The half-life of the monoclonal was 63–73 days, compared to that of palivizumab (19–27 days).<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> At day 151 (5 months), 87% of the children who received a 50 mg dose had antibody concentrations above 90% of the concentration considered effective (6.8 μg/ml) and 90% had an increase of at least 4 titres from their baseline concentration prior to the start of the trial. Three of the monoclonal recipients had serious adverse effects (RSV lower respiratory tract infection and febrile seizures). Anti-drug antibodies were detected at any time-point in 28.2% of monoclonal recipients and in 26.5% at day 361; no adverse effects associated with this type of antimonoclonal antibody were detected. In this study the authors confirm efficacy, safety, and durability (up to 5 months) in the prevention of RSV in preterm infants with the monoclonal antibody MEDI8897.<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a></p><p id="p0075" class="elsevierStylePara elsevierViewall">Griffin et al.<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a> conducted a clinical trial on the efficacy of the monoclonal nirsevimab (MEDI8897) in the prevention of lower respiratory tract infections caused by RSV in healthy preterm infants (29–34 weeks of life). They were divided into 2 groups: administration of the monoclonal at a dose of 50 mg single intramuscular injection vs. placebo at the beginning of the seasonal RSV epidemic. The mean incidence of RSV lower respiratory tract infections was 70.1% lower in the nirsevimab group than in the placebo group. Likewise, the incidence of hospitalisation for RSV was 78.4% lower in the monoclonal group than in the placebo group. These differences remained almost constant throughout the 150 days of follow-up after administration of the monoclonal antibody.</p><p id="p0080" class="elsevierStylePara elsevierViewall">Nirsevimab has been shown capable of neutralising both RSV-A and RSV-B; this data is important because another monoclonal antibody (suptavumab) in a clinical trial (<a href="http://ClinicalTrials.org">ClinicalTrials.org</a> number <a href="ctgov:NCT02325791">NCT02325791</a>) was not capable of neutralising RSV-B in vitro because it targeted site V of the RSV pre-F protein.<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a></p><p id="p0085" class="elsevierStylePara elsevierViewall">Hammitt et al.<a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a> presented the results of the phase 3 randomised clinical trial (MELODY study) testing the safety and prevention capacity of nirsevimab in late preterm and healthy term infants. A total of 994 infants were studied, who received a single dose of 50 mg (if they weighed <<span class="elsevierStyleHsp" style=""></span>5 kg or 100 mg if they weighed 5 kg) of the monoclonal antibody in a single injection versus 496 infants who were given a placebo. RSV-associated lower respiratory tract infections presented in 1.2% of the monoclonal antibody receptors compared to 5% of the placebo group; these data imply an efficacy of 74.5% for the monoclonal antibody (p < .001). Of the monoclonal antibody group, 0.6% versus 1.6% of the control group had RSV-associated hospitalisations, with a preventive efficacy of 62.1%, although without a significant difference (p = .07). All these data are very much in line with those obtained by Griffin et al.<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a> in healthy preterm infants.</p><p id="p0090" class="elsevierStylePara elsevierViewall">The safety, tolerability, and efficacy of nirsevimab compared to palivizumab have also been studied in a phase 2/3 clinical trial in infants with congenital heart disease, chronic lung disease, and preterm infants <<span class="elsevierStyleHsp" style=""></span>35 weeks gestation.<a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a> RSV-associated lower respiratory tract disease was observed in 0.6% of the nirsevimab group versus 1% of the palivizumab group. Nirsevimab levels remained above therapeutic levels throughout the 150-day study. Antimonoclonal antibodies were detected in 0.4% of nirsevimab recipients versus 3.6% of palivizumab recipients.</p><p id="p0095" class="elsevierStylePara elsevierViewall">All these studies seem to indicate the high efficacy and safety of nirsevimab in preventing both RSV-associated disease and hospital admissions in healthy preterm and term infants with previous cardiopulmonary disease.<a class="elsevierStyleCrossRefs" href="#bb0135"><span class="elsevierStyleSup">27–29</span></a> The monoclonal injected in a single 50 mg dose maintains protective levels for a minimum period of 5 months and can be administered at the beginning of the RSV epidemic season.</p><p id="p0100" class="elsevierStylePara elsevierViewall">If the cost of the new monoclonal were cost-competitive, universal immunisation of the entire child population (vaccine-like strategy) at the beginning of the RSV epidemic season could be proposed. Some could be immunised at birth during the months of the epidemic (hospital vaccination) and the rest at the beginning of the epidemic (primary care).<a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a> This would lead to a very significant reduction in lower respiratory tract infections (bronchiolitis) and hospital admissions caused by RSV, with consequent savings in healthcare costs.<a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a></p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Funding</span><p id="p0105" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1855528" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "as0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1613254" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1855527" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "as0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1613253" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "s0010" "titulo" => "Characteristics of respiratory syncytial virus" ] 6 => array:2 [ "identificador" => "s0015" "titulo" => "Humanised monoclonal antibodies" ] 7 => array:2 [ "identificador" => "s0020" "titulo" => "Nirsevimab" ] 8 => array:2 [ "identificador" => "s0025" "titulo" => "Funding" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-10-07" "fechaAceptado" => "2023-12-29" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1613254" "palabras" => array:4 [ 0 => "Respiratory syncytial virus" 1 => "Monoclonal antibodies" 2 => "Nirsevimab" 3 => "Immunisation" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1613253" "palabras" => array:4 [ 0 => "Virus respiratorio sincitial" 1 => "Anticuerpos monoclonales" 2 => "Nirsevimab" 3 => "Inmunización" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Respiratory Syncytial Virus (RSV) causes epidemic acute respiratory pathologies especially in young children and the elderly. There is currently no effective vaccine against this virus. An alternative to prevent RSV disease is passive immunoprophylaxis through the administration of neutralising antibodies. In 2002, palivizumab was approved for children at risk of RSV. However, its high cost and its monthly administration do not allow it to be used as universal prophylaxis. In 2017, the monoclonal antibody nirsevimab, which has a power and activity 50 times higher than palivizumab, was described as having a half-life of at least 5 months. Clinical trials have shown the efficacy and safety of nirsevimab in preventing both the disease and hospital admissions associated with RSV in premature and full-term infants, both healthy and with previous cardiopulmonary pathologies. With this monoclonal antibody, universal immunisation is feasible (vaccine-like strategy).</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="as0010" class="elsevierStyleSection elsevierViewall"><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">El Virus Respiratorio Sincitial (VRS) es el causante de patologías respiratorias agudas epidémicas. Actualmente no existe una vacuna eficaz frente a este virus. Una alternativa para prevenir la enfermedad por VRS es la inmunoprofilaxis pasiva mediante la administración de anticuerpos neutralizantes. En 2002 se aprobó el palivizumab para los niños de riesgo frente al VRS. Sin embargo, el elevado coste y su administración mensual, no permite utilizarlo como profilaxis universal. En 2017 se describió el monoclonal nirsevimab, que presenta una potencia y actividad 50 veces superior al palivizumab con una vida media de cómo mínimo 5 meses. Los ensayos clínicos han mostrado la eficacia y seguridad de nirsevimab en la prevención tanto de la enfermedad como en los ingresos hospitalarios asociados al VRS de los prematuros y nacidos a término tanto sanos como con patologías cardiopulmonares previas. Con este monoclonal podría realizarse una inmunización universal (vaccine-like strategy).</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="np4005">Please cite this article as: Reina J, Iglesias C. Nirsevimab: hacia la inmunización universal de la población infantil frente al virus respiratorio sincitial. Vacun. 2022. <span class="elsevierStyleInterRef" id="ir3005" href="https://doi.org/10.1016/j.vacun.2022.10.002">https://doi.org/10.1016/j.vacun.2022.10.002</span></p>" ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 911 "Ancho" => 1327 "Tamanyo" => 69702 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Diagram of the external and internal structure of respiratory syncytial virus (modified from Plemper et al.<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>).</p>" ] ] 1 => array:8 [ "identificador" => "f0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1341 "Ancho" => 1713 "Tamanyo" => 152789 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Diagram of IgG processing through binding to the FCRn receptor located on the cell surface (modified from Roopenian et al.<a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a>).</p>" ] ] 2 => array:8 [ "identificador" => "f0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 995 "Ancho" => 1575 "Tamanyo" => 87054 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Mutations introduced in the CH2 part of the heavy chain of the Fc fragment to increase affinity for the FcRn receptor and extend the half-life of monoclonal antibodies (modified from Robbie et al.<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a>).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." 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