Broad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells

ABSTRACT Although most seasonal inactivated influenza vaccines (IIV) contain neuraminidase (NA), the extent and mechanisms of action of protective human NA-specific humoral responses induced by vaccination are poorly resolved. Due to the propensity of influenza virus for antigenic drift and shift an...

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Autores principales:	Michael S. Piepenbrink, Aitor Nogales, Madhubanti Basu, Christopher F. Fucile, Jane L. Liesveld, Michael C. Keefer, Alexander F. Rosenberg, Luis Martinez-Sobrido, James J. Kobie
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	B cell responses human influenza vaccines monoclonal antibodies neuraminidase Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/486dc477ed854784addaf977de56a6bc
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spelling	oai:doaj.org-article:486dc477ed854784addaf977de56a6bc2021-11-15T15:55:25ZBroad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells10.1128/mBio.00066-192150-7511https://doaj.org/article/486dc477ed854784addaf977de56a6bc2019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00066-19https://doaj.org/toc/2150-7511ABSTRACT Although most seasonal inactivated influenza vaccines (IIV) contain neuraminidase (NA), the extent and mechanisms of action of protective human NA-specific humoral responses induced by vaccination are poorly resolved. Due to the propensity of influenza virus for antigenic drift and shift and its tendency to elicit predominantly strain-specific antibodies, humanity remains susceptible to waves of new strains of seasonal viruses and is at risk from viruses with pandemic potential for which limited or no immunity may exist. Here we demonstrate that the use of IIV results in increased levels of influenza B virus (IBV) NA-specific serum antibodies. Detailed analysis of the IBV NA B cell response indicates concurrent expansion of IBV NA-specific peripheral blood plasmablasts 7 days after IIV immunization which express monoclonal antibodies with broad and potent antiviral activity against both IBV Victoria and Yamagata lineages and prophylactic and therapeutic activity in mice. These IBV NA-specific B cell clonal lineages persisted in CD138+ long-lived bone marrow plasma cells. These results represent the first demonstration that IIV-induced NA human antibodies can protect and treat influenza virus infection in vivo and suggest that IIV can induce a subset of IBV NA-specific B cells with broad protective potential, a feature that warrants further study for universal influenza vaccine development. IMPORTANCE Influenza virus infections continue to cause substantial morbidity and mortality despite the availability of seasonal vaccines. The extensive genetic variability in seasonal and potentially pandemic influenza strains necessitates new vaccine strategies that can induce universal protection by focusing the immune response on generating protective antibodies against conserved targets such as regions within the influenza neuraminidase protein. We have demonstrated that seasonal immunization stimulates neuraminidase-specific antibodies in humans that are broad and potent in their protection from influenza B virus when tested in mice. These antibodies further persist in the bone marrow, where they are expressed by long-lived antibody-producing cells, referred to here as plasma cells. The significance in our research is the demonstration that seasonal influenza immunization can induce a subset of neuraminidase-specific B cells with broad protective potential, a process that if further studied and enhanced could aid in the development of a universal influenza vaccine.Michael S. PiepenbrinkAitor NogalesMadhubanti BasuChristopher F. FucileJane L. LiesveldMichael C. KeeferAlexander F. RosenbergLuis Martinez-SobridoJames J. KobieAmerican Society for MicrobiologyarticleB cell responseshumaninfluenza vaccinesmonoclonal antibodiesneuraminidaseMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	B cell responses human influenza vaccines monoclonal antibodies neuraminidase Microbiology QR1-502
spellingShingle	B cell responses human influenza vaccines monoclonal antibodies neuraminidase Microbiology QR1-502 Michael S. Piepenbrink Aitor Nogales Madhubanti Basu Christopher F. Fucile Jane L. Liesveld Michael C. Keefer Alexander F. Rosenberg Luis Martinez-Sobrido James J. Kobie Broad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells
description	ABSTRACT Although most seasonal inactivated influenza vaccines (IIV) contain neuraminidase (NA), the extent and mechanisms of action of protective human NA-specific humoral responses induced by vaccination are poorly resolved. Due to the propensity of influenza virus for antigenic drift and shift and its tendency to elicit predominantly strain-specific antibodies, humanity remains susceptible to waves of new strains of seasonal viruses and is at risk from viruses with pandemic potential for which limited or no immunity may exist. Here we demonstrate that the use of IIV results in increased levels of influenza B virus (IBV) NA-specific serum antibodies. Detailed analysis of the IBV NA B cell response indicates concurrent expansion of IBV NA-specific peripheral blood plasmablasts 7 days after IIV immunization which express monoclonal antibodies with broad and potent antiviral activity against both IBV Victoria and Yamagata lineages and prophylactic and therapeutic activity in mice. These IBV NA-specific B cell clonal lineages persisted in CD138+ long-lived bone marrow plasma cells. These results represent the first demonstration that IIV-induced NA human antibodies can protect and treat influenza virus infection in vivo and suggest that IIV can induce a subset of IBV NA-specific B cells with broad protective potential, a feature that warrants further study for universal influenza vaccine development. IMPORTANCE Influenza virus infections continue to cause substantial morbidity and mortality despite the availability of seasonal vaccines. The extensive genetic variability in seasonal and potentially pandemic influenza strains necessitates new vaccine strategies that can induce universal protection by focusing the immune response on generating protective antibodies against conserved targets such as regions within the influenza neuraminidase protein. We have demonstrated that seasonal immunization stimulates neuraminidase-specific antibodies in humans that are broad and potent in their protection from influenza B virus when tested in mice. These antibodies further persist in the bone marrow, where they are expressed by long-lived antibody-producing cells, referred to here as plasma cells. The significance in our research is the demonstration that seasonal influenza immunization can induce a subset of neuraminidase-specific B cells with broad protective potential, a process that if further studied and enhanced could aid in the development of a universal influenza vaccine.
format	article
author	Michael S. Piepenbrink Aitor Nogales Madhubanti Basu Christopher F. Fucile Jane L. Liesveld Michael C. Keefer Alexander F. Rosenberg Luis Martinez-Sobrido James J. Kobie
author_facet	Michael S. Piepenbrink Aitor Nogales Madhubanti Basu Christopher F. Fucile Jane L. Liesveld Michael C. Keefer Alexander F. Rosenberg Luis Martinez-Sobrido James J. Kobie
author_sort	Michael S. Piepenbrink
title	Broad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells
title_short	Broad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells
title_full	Broad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells
title_fullStr	Broad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells
title_full_unstemmed	Broad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells
title_sort	broad and protective influenza b virus neuraminidase antibodies in humans after vaccination and their clonal persistence as plasma cells
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/486dc477ed854784addaf977de56a6bc
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Broad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells

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