Broadly Cross-Reactive, Nonneutralizing Antibodies against Influenza B Virus Hemagglutinin Demonstrate Effector Function-Dependent Protection against Lethal Viral Challenge in Mice

Protection from influenza virus infection is canonically associated with antibodies that neutralize the virus by blocking the interaction between the viral hemagglutinin and host cell receptors. However, protection can also be conferred by other mechanisms, including antibody-mediated effector funct...

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Detalles Bibliográficos
Autores: Arunkumar, Guha Asthagiri, Ioannou, Andriani, Wohlbold, Teddy John, Meade, Philip, Aslam, Sadaf, Amanat, Fatima, Ayllón Barasoain, Juan, García Sastre, Adolfo, Krammer, Florian
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Universidad de Burgos (UBU)
Repositorio:Repositorio Institucional de la Universidad de Burgos (RIUBU)
OAI Identifier:oai:riubu.ubu.es:10259/10928
Acceso en línea:https://hdl.handle.net/10259/10928
Access Level:acceso abierto
Palabra clave:ADCC
HA
Influenza B
MAb
Gripe
Influenza
Descripción
Sumario:Protection from influenza virus infection is canonically associated with antibodies that neutralize the virus by blocking the interaction between the viral hemagglutinin and host cell receptors. However, protection can also be conferred by other mechanisms, including antibody-mediated effector functions. Here, we report the characterization of 22 broadly cross-reactive, nonneutralizing antibodies specific for influenza B virus hemagglutinin. The majority of these antibodies recognized influenza B viruses isolated over the period of 73 years and bind the conserved stalk domain of the hemagglutinin. A proportion of the characterized antibodies protected mice from both morbidity and mortality after challenge with a lethal dose of influenza B virus. Activity in an antibody-dependent cell-mediated cytotoxicity reporter assay correlated strongly with protection, suggesting that Fc-dependent effector function determines protective efficacy. The information regarding mechanism of action and epitope location stemming from our characterization of these antibodies will inform the design of urgently needed vaccines that could induce broad protection against influenza B viruses.