Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies

ABSTRACT Influenza virus neuraminidase (NA) has been under intense study recently as a vaccine antigen, yet there remain unanswered questions regarding the immune response directed toward NA. Antibodies (Abs) that can inhibit NA activity have been shown to aid in the control of disease caused by inf...

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Autores principales:	E. R. Job, T. Ysenbaert, A. Smet, A. Van Hecke, L. Meuris, H. Kleanthous, X. Saelens, T. U. Vogel
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	influenza neuraminidase Fcγ receptor antibodies influenza vaccines Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7d9069626bfa4f5f9bd82345c4070ea2
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spelling	oai:doaj.org-article:7d9069626bfa4f5f9bd82345c4070ea22021-11-15T15:59:40ZFcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies10.1128/mBio.01667-192150-7511https://doaj.org/article/7d9069626bfa4f5f9bd82345c4070ea22019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01667-19https://doaj.org/toc/2150-7511ABSTRACT Influenza virus neuraminidase (NA) has been under intense study recently as a vaccine antigen, yet there remain unanswered questions regarding the immune response directed toward NA. Antibodies (Abs) that can inhibit NA activity have been shown to aid in the control of disease caused by influenza virus infection in humans and animal models, yet how and if interactions between the Fc portion of anti-NA Abs and Fcγ receptors (FcγR) contribute to protection has not yet been extensively studied. Herein, we show that poly- and monoclonal anti-NA IgG antibodies with NA inhibitory activity can control A(H1N1)pdm09 infection in the absence of FcγRs, but FcγR interaction aided in viral clearance from the lungs. In contrast, a mouse-human chimeric anti-NA IgG1 that was incapable of mediating NA inhibition (NI) solely relied on FcγR interaction to protect transgenic mice (with a humanized FcγR compartment) against A(H1N1)pdm09 infection. As such, this study suggests that NA-specific antibodies contribute to protection against influenza A virus infection even in the absence of NI activity and supports protection through multiple effector mechanisms. IMPORTANCE There is a pressing need for next-generation influenza vaccine strategies that are better able to manage antigenic drift and the cocirculation of multiple drift variants and that consistently improve vaccine effectiveness. Influenza virus NA is a key target antigen as a component of a next-generation vaccine in the influenza field, with evidence for a role in protective immunity in humans. However, mechanisms of protection provided by antibodies directed to NA remain largely unexplored. Herein, we show that antibody Fc interaction with Fcγ receptors (FcγRs) expressed on effector cells contributes to viral control in a murine model of influenza. Importantly, a chimeric mouse-human IgG1 with no direct antiviral activity was demonstrated to solely rely on FcγRs to protect mice from disease. Therefore, antibodies without NA enzymatic inhibitory activity may also play a role in controlling influenza viruses and should be of consideration when designing NA-based vaccines and assessing immunogenicity.E. R. JobT. YsenbaertA. SmetA. Van HeckeL. MeurisH. KleanthousX. SaelensT. U. VogelAmerican Society for MicrobiologyarticleinfluenzaneuraminidaseFcγ receptorantibodiesinfluenza vaccinesMicrobiologyQR1-502ENmBio, Vol 10, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	influenza neuraminidase Fcγ receptor antibodies influenza vaccines Microbiology QR1-502
spellingShingle	influenza neuraminidase Fcγ receptor antibodies influenza vaccines Microbiology QR1-502 E. R. Job T. Ysenbaert A. Smet A. Van Hecke L. Meuris H. Kleanthous X. Saelens T. U. Vogel Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies
description	ABSTRACT Influenza virus neuraminidase (NA) has been under intense study recently as a vaccine antigen, yet there remain unanswered questions regarding the immune response directed toward NA. Antibodies (Abs) that can inhibit NA activity have been shown to aid in the control of disease caused by influenza virus infection in humans and animal models, yet how and if interactions between the Fc portion of anti-NA Abs and Fcγ receptors (FcγR) contribute to protection has not yet been extensively studied. Herein, we show that poly- and monoclonal anti-NA IgG antibodies with NA inhibitory activity can control A(H1N1)pdm09 infection in the absence of FcγRs, but FcγR interaction aided in viral clearance from the lungs. In contrast, a mouse-human chimeric anti-NA IgG1 that was incapable of mediating NA inhibition (NI) solely relied on FcγR interaction to protect transgenic mice (with a humanized FcγR compartment) against A(H1N1)pdm09 infection. As such, this study suggests that NA-specific antibodies contribute to protection against influenza A virus infection even in the absence of NI activity and supports protection through multiple effector mechanisms. IMPORTANCE There is a pressing need for next-generation influenza vaccine strategies that are better able to manage antigenic drift and the cocirculation of multiple drift variants and that consistently improve vaccine effectiveness. Influenza virus NA is a key target antigen as a component of a next-generation vaccine in the influenza field, with evidence for a role in protective immunity in humans. However, mechanisms of protection provided by antibodies directed to NA remain largely unexplored. Herein, we show that antibody Fc interaction with Fcγ receptors (FcγRs) expressed on effector cells contributes to viral control in a murine model of influenza. Importantly, a chimeric mouse-human IgG1 with no direct antiviral activity was demonstrated to solely rely on FcγRs to protect mice from disease. Therefore, antibodies without NA enzymatic inhibitory activity may also play a role in controlling influenza viruses and should be of consideration when designing NA-based vaccines and assessing immunogenicity.
format	article
author	E. R. Job T. Ysenbaert A. Smet A. Van Hecke L. Meuris H. Kleanthous X. Saelens T. U. Vogel
author_facet	E. R. Job T. Ysenbaert A. Smet A. Van Hecke L. Meuris H. Kleanthous X. Saelens T. U. Vogel
author_sort	E. R. Job
title	Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies
title_short	Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies
title_full	Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies
title_fullStr	Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies
title_full_unstemmed	Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies
title_sort	fcγ receptors contribute to the antiviral properties of influenza virus neuraminidase-specific antibodies
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/7d9069626bfa4f5f9bd82345c4070ea2
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Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies

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