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J Virol. 2019 Jan 9. pii: JVI.01696-18. doi: 10.1128/JVI.01696-18. [Epub ahead of print]
Broadly cross-reactive, non-neutralizing antibodies against the influenza B virus hemagglutinin demonstrate effector function dependent protection against lethal viral challenge in mice.
Arunkumar GA1,2, Ioannou A1, Wohlbold TJ1,2, Meade P1,2, Aslam S1, Amanat F1,2, Ayllon J1, Garc?a-Sastre A1,3,4, Krammer F5.
Author information
Abstract
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, non-neutralizing 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.IMPORTANCE While broadly protective antibodies against the influenza A virus hemagglutinin have been well studied, very limited information is available for similar antibodies that recognize influenza B viruses. Similarly, the development of a universal or broadly protective influenza B virus vaccine lags behind the development of such a vaccine for influenza A virus. More information about epitope location and mechanism of action of broadly protective influenza B virus antibodies is required to inform vaccine development. In addition, protective antibodies could be a useful tool to treat or prevent influenza B virus infection in pediatric cohorts or in a therapeutic setting in immunocompromised individuals in conjugation with existing treatment avenues.
Copyright ? 2019 American Society for Microbiology.
PMID: 30626682 DOI: 10.1128/JVI.01696-18
Broadly cross-reactive, non-neutralizing antibodies against the influenza B virus hemagglutinin demonstrate effector function dependent protection against lethal viral challenge in mice.
Arunkumar GA1,2, Ioannou A1, Wohlbold TJ1,2, Meade P1,2, Aslam S1, Amanat F1,2, Ayllon J1, Garc?a-Sastre A1,3,4, Krammer F5.
Author information
Abstract
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, non-neutralizing 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.IMPORTANCE While broadly protective antibodies against the influenza A virus hemagglutinin have been well studied, very limited information is available for similar antibodies that recognize influenza B viruses. Similarly, the development of a universal or broadly protective influenza B virus vaccine lags behind the development of such a vaccine for influenza A virus. More information about epitope location and mechanism of action of broadly protective influenza B virus antibodies is required to inform vaccine development. In addition, protective antibodies could be a useful tool to treat or prevent influenza B virus infection in pediatric cohorts or in a therapeutic setting in immunocompromised individuals in conjugation with existing treatment avenues.
Copyright ? 2019 American Society for Microbiology.
PMID: 30626682 DOI: 10.1128/JVI.01696-18