Broadly cross-reactive, nonneutralizing antibodies against influenza B virus hemagglutinin demonstrate effector function-dependent protection against lethal viral challenge in mice

Guha Asthagiri Arunkumar, Andriani Ioannou, Teddy John Wohlbold, Philip Meade, Sadaf Aslam, Fatima Amanat, Juan Ayllon, Adolfo García-Sastre, Florian Krammer

Research output: Contribution to journalArticle

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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, 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. IMPORTANCE While broadly protective antibodies against the influenza A virus hemagglutinin have been well studied, very limited information is available for antibodies that broadly 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.

Original languageEnglish
Article numbere01696-18
JournalJournal of Virology
Volume93
Issue number6
DOIs
Publication statusPublished - 01-03-2019

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Influenza B virus
Hemagglutinins
hemagglutinins
antibodies
Antibodies
mice
Vaccines
Influenza A virus
Virus Diseases
vaccine development
Epitopes
epitopes
Viral Hemagglutinins
mechanism of action
Antibody-Dependent Cell Cytotoxicity
vaccines
immunocompromised population
Influenza Vaccines
Orthomyxoviridae
lethal dose

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Arunkumar, Guha Asthagiri ; Ioannou, Andriani ; Wohlbold, Teddy John ; Meade, Philip ; Aslam, Sadaf ; Amanat, Fatima ; Ayllon, Juan ; García-Sastre, Adolfo ; Krammer, Florian. / Broadly cross-reactive, nonneutralizing antibodies against influenza B virus hemagglutinin demonstrate effector function-dependent protection against lethal viral challenge in mice. In: Journal of Virology. 2019 ; Vol. 93, No. 6.
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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, 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. IMPORTANCE While broadly protective antibodies against the influenza A virus hemagglutinin have been well studied, very limited information is available for antibodies that broadly 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.",
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Broadly cross-reactive, nonneutralizing antibodies against influenza B virus hemagglutinin demonstrate effector function-dependent protection against lethal viral challenge in mice. / Arunkumar, Guha Asthagiri; Ioannou, Andriani; Wohlbold, Teddy John; Meade, Philip; Aslam, Sadaf; Amanat, Fatima; Ayllon, Juan; García-Sastre, Adolfo; Krammer, Florian.

In: Journal of Virology, Vol. 93, No. 6, e01696-18, 01.03.2019.

Research output: Contribution to journalArticle

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AU - Arunkumar, Guha Asthagiri

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AU - Wohlbold, Teddy John

AU - Meade, Philip

AU - Aslam, Sadaf

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AU - Ayllon, Juan

AU - García-Sastre, Adolfo

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