Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs

ABSTRACT Despite efforts to control influenza virus infection and transmission, influenza viruses still cause significant morbidity and mortality in the global human population each year. Most of the current vaccines target the immunodominant hemagglutinin surface glycoprotein of the virus. However,...

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Autores principales:	Meagan McMahon, Ericka Kirkpatrick, Daniel Stadlbauer, Shirin Strohmeier, Nicole M. Bouvier, Florian Krammer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	influenza influenza B neuraminidase transmission vaccine Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cec8869cb1464518a4ade673a0a88bb8
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spelling	oai:doaj.org-article:cec8869cb1464518a4ade673a0a88bb82021-11-15T15:55:23ZMucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs10.1128/mBio.00560-192150-7511https://doaj.org/article/cec8869cb1464518a4ade673a0a88bb82019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00560-19https://doaj.org/toc/2150-7511ABSTRACT Despite efforts to control influenza virus infection and transmission, influenza viruses still cause significant morbidity and mortality in the global human population each year. Most of the current vaccines target the immunodominant hemagglutinin surface glycoprotein of the virus. However, reduced severity of disease and viral shedding have also been linked to antibodies targeting the second viral surface glycoprotein, the neuraminidase. Importantly, antineuraminidase immunity was shown to be relatively broad, in contrast to vaccine-induced antibodies to the hemagglutinin head domain. In this study, we assessed recombinant neuraminidase protein vaccination for its ability to prevent or limit virus transmission. We vaccinated guinea pigs either intramuscularly or intranasally with a recombinant influenza B virus neuraminidase to assess whether neuraminidase vaccination via these routes could prevent transmission of the homologous virus to a naive recipient. Guinea pigs vaccinated with neuraminidase showed reduced virus titers; however, only vaccination via the intranasal route fully prevented virus transmission to naive animals. We found high levels of antineuraminidase antibodies capable of inhibiting neuraminidase enzymatic activity in the nasal washes of intranasally vaccinated animals, which may explain the observed differences in transmission. We also determined that mucosal immunity to neuraminidase impaired the transmission efficiency of a heterologous influenza B virus, although to a lesser extent. Finally, we found that neuraminidase-vaccinated animals were still susceptible to infection via the airborne and contact transmission routes. However, significantly lower virus titers were detected in these vaccinated recipients. In summary, our data suggest that supplementing vaccine formulations with neuraminidase and vaccinating via the intranasal route may broadly prevent transmission of influenza B viruses. IMPORTANCE Recently, the protective effect of anti-neuraminidase immunity has been highlighted by several studies in humans and animal models. However, so far the role that anti-neuraminidase immunity plays in inhibition of virus transmission has not been explored. In addition, neuraminidase has been ignored as an antigen for influenza virus vaccines. We show here that neuraminidase-based vaccines can inhibit the transmission of influenza virus. Therefore, neuraminidase should be considered as an antigen for improved influenza virus vaccines that not only protect individuals from disease but also inhibit further spread of the virus in the population.Meagan McMahonEricka KirkpatrickDaniel StadlbauerShirin StrohmeierNicole M. BouvierFlorian KrammerAmerican Society for Microbiologyarticleinfluenzainfluenza BneuraminidasetransmissionvaccineMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	influenza influenza B neuraminidase transmission vaccine Microbiology QR1-502
spellingShingle	influenza influenza B neuraminidase transmission vaccine Microbiology QR1-502 Meagan McMahon Ericka Kirkpatrick Daniel Stadlbauer Shirin Strohmeier Nicole M. Bouvier Florian Krammer Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs
description	ABSTRACT Despite efforts to control influenza virus infection and transmission, influenza viruses still cause significant morbidity and mortality in the global human population each year. Most of the current vaccines target the immunodominant hemagglutinin surface glycoprotein of the virus. However, reduced severity of disease and viral shedding have also been linked to antibodies targeting the second viral surface glycoprotein, the neuraminidase. Importantly, antineuraminidase immunity was shown to be relatively broad, in contrast to vaccine-induced antibodies to the hemagglutinin head domain. In this study, we assessed recombinant neuraminidase protein vaccination for its ability to prevent or limit virus transmission. We vaccinated guinea pigs either intramuscularly or intranasally with a recombinant influenza B virus neuraminidase to assess whether neuraminidase vaccination via these routes could prevent transmission of the homologous virus to a naive recipient. Guinea pigs vaccinated with neuraminidase showed reduced virus titers; however, only vaccination via the intranasal route fully prevented virus transmission to naive animals. We found high levels of antineuraminidase antibodies capable of inhibiting neuraminidase enzymatic activity in the nasal washes of intranasally vaccinated animals, which may explain the observed differences in transmission. We also determined that mucosal immunity to neuraminidase impaired the transmission efficiency of a heterologous influenza B virus, although to a lesser extent. Finally, we found that neuraminidase-vaccinated animals were still susceptible to infection via the airborne and contact transmission routes. However, significantly lower virus titers were detected in these vaccinated recipients. In summary, our data suggest that supplementing vaccine formulations with neuraminidase and vaccinating via the intranasal route may broadly prevent transmission of influenza B viruses. IMPORTANCE Recently, the protective effect of anti-neuraminidase immunity has been highlighted by several studies in humans and animal models. However, so far the role that anti-neuraminidase immunity plays in inhibition of virus transmission has not been explored. In addition, neuraminidase has been ignored as an antigen for influenza virus vaccines. We show here that neuraminidase-based vaccines can inhibit the transmission of influenza virus. Therefore, neuraminidase should be considered as an antigen for improved influenza virus vaccines that not only protect individuals from disease but also inhibit further spread of the virus in the population.
format	article
author	Meagan McMahon Ericka Kirkpatrick Daniel Stadlbauer Shirin Strohmeier Nicole M. Bouvier Florian Krammer
author_facet	Meagan McMahon Ericka Kirkpatrick Daniel Stadlbauer Shirin Strohmeier Nicole M. Bouvier Florian Krammer
author_sort	Meagan McMahon
title	Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs
title_short	Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs
title_full	Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs
title_fullStr	Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs
title_full_unstemmed	Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs
title_sort	mucosal immunity against neuraminidase prevents influenza b virus transmission in guinea pigs
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/cec8869cb1464518a4ade673a0a88bb8
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Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs

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