Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin

ABSTRACT Antibody responses to influenza virus hemagglutinin provide protection against infection and are well studied. Less is known about the human antibody responses to the second surface glycoprotein, neuraminidase. Here, we assessed human antibody reactivity to a panel of N1, N2, and influenza...

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Autores principales:	Madhusudan Rajendran, Raffael Nachbagauer, Megan E. Ermler, Paul Bunduc, Fatima Amanat, Ruvim Izikson, Manon Cox, Peter Palese, Maryna Eichelberger, Florian Krammer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	influenza influenza virus neuraminidase neuraminidase inhibition Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7c9329d833a84c95bbc4fca196652c5c
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spelling	oai:doaj.org-article:7c9329d833a84c95bbc4fca196652c5c2021-11-15T15:50:59ZAnalysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin10.1128/mBio.02281-162150-7511https://doaj.org/article/7c9329d833a84c95bbc4fca196652c5c2017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02281-16https://doaj.org/toc/2150-7511ABSTRACT Antibody responses to influenza virus hemagglutinin provide protection against infection and are well studied. Less is known about the human antibody responses to the second surface glycoprotein, neuraminidase. Here, we assessed human antibody reactivity to a panel of N1, N2, and influenza B virus neuraminidases in different age groups, including children, adults, and the elderly. Using enzyme-linked immunosorbent assays (ELISA), we determined the breadth, magnitude, and isotype distribution of neuraminidase antibody responses to historic, current, and avian strains, as well as to recent isolates to which these individuals have not been exposed. It appears that antibody levels against N1 neuraminidases were lower than those against N2 or B neuraminidases. The anti-neuraminidase antibody levels increased with age and were, in general, highest against strains that circulated during the childhood of the tested individuals, providing evidence for “original antigenic sin.” Titers measured by ELISA correlated well with titers measured by the neuraminidase inhibition assays. However, in the case of the 2009 pandemic H1N1 virus, we found evidence of interference from antibodies binding to the conserved stalk domain of the hemagglutinin. In conclusion, we found that antibodies against the neuraminidase differ in magnitude and breadth between subtypes and age groups in the human population. (This study has been registered at ClinicalTrials.gov under registration no. NCT00336453, NCT00539981, and NCT00395174.) IMPORTANCE Anti-neuraminidase antibodies can afford broad protection from influenza virus infection in animal models and humans. However, little is known about the breadth and magnitude of the anti-neuraminidase response in the human population. Here we assessed antibody levels of children, adults, and the elderly against a panel of N1, N2, and type B influenza virus neuraminidases. We demonstrated that antibody levels measured by ELISA correlate well with functional neuraminidase inhibition titers. This is an important finding since ELISA is a simpler method than functional assays and can be implemented in high-throughput settings to analyze large numbers of samples. Furthermore, we showed that low titers of broadly cross-reactive antibodies against neuraminidase are prevalent in humans. By the use of an appropriate vaccination strategy, these titers could potentially be boosted to levels that might provide broad protection from influenza virus infection.Madhusudan RajendranRaffael NachbagauerMegan E. ErmlerPaul BunducFatima AmanatRuvim IziksonManon CoxPeter PaleseMaryna EichelbergerFlorian KrammerAmerican Society for Microbiologyarticleinfluenzainfluenza virusneuraminidaseneuraminidase inhibitionMicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	influenza influenza virus neuraminidase neuraminidase inhibition Microbiology QR1-502
spellingShingle	influenza influenza virus neuraminidase neuraminidase inhibition Microbiology QR1-502 Madhusudan Rajendran Raffael Nachbagauer Megan E. Ermler Paul Bunduc Fatima Amanat Ruvim Izikson Manon Cox Peter Palese Maryna Eichelberger Florian Krammer Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin
description	ABSTRACT Antibody responses to influenza virus hemagglutinin provide protection against infection and are well studied. Less is known about the human antibody responses to the second surface glycoprotein, neuraminidase. Here, we assessed human antibody reactivity to a panel of N1, N2, and influenza B virus neuraminidases in different age groups, including children, adults, and the elderly. Using enzyme-linked immunosorbent assays (ELISA), we determined the breadth, magnitude, and isotype distribution of neuraminidase antibody responses to historic, current, and avian strains, as well as to recent isolates to which these individuals have not been exposed. It appears that antibody levels against N1 neuraminidases were lower than those against N2 or B neuraminidases. The anti-neuraminidase antibody levels increased with age and were, in general, highest against strains that circulated during the childhood of the tested individuals, providing evidence for “original antigenic sin.” Titers measured by ELISA correlated well with titers measured by the neuraminidase inhibition assays. However, in the case of the 2009 pandemic H1N1 virus, we found evidence of interference from antibodies binding to the conserved stalk domain of the hemagglutinin. In conclusion, we found that antibodies against the neuraminidase differ in magnitude and breadth between subtypes and age groups in the human population. (This study has been registered at ClinicalTrials.gov under registration no. NCT00336453, NCT00539981, and NCT00395174.) IMPORTANCE Anti-neuraminidase antibodies can afford broad protection from influenza virus infection in animal models and humans. However, little is known about the breadth and magnitude of the anti-neuraminidase response in the human population. Here we assessed antibody levels of children, adults, and the elderly against a panel of N1, N2, and type B influenza virus neuraminidases. We demonstrated that antibody levels measured by ELISA correlate well with functional neuraminidase inhibition titers. This is an important finding since ELISA is a simpler method than functional assays and can be implemented in high-throughput settings to analyze large numbers of samples. Furthermore, we showed that low titers of broadly cross-reactive antibodies against neuraminidase are prevalent in humans. By the use of an appropriate vaccination strategy, these titers could potentially be boosted to levels that might provide broad protection from influenza virus infection.
format	article
author	Madhusudan Rajendran Raffael Nachbagauer Megan E. Ermler Paul Bunduc Fatima Amanat Ruvim Izikson Manon Cox Peter Palese Maryna Eichelberger Florian Krammer
author_facet	Madhusudan Rajendran Raffael Nachbagauer Megan E. Ermler Paul Bunduc Fatima Amanat Ruvim Izikson Manon Cox Peter Palese Maryna Eichelberger Florian Krammer
author_sort	Madhusudan Rajendran
title	Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin
title_short	Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin
title_full	Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin
title_fullStr	Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin
title_full_unstemmed	Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin
title_sort	analysis of anti-influenza virus neuraminidase antibodies in children, adults, and the elderly by elisa and enzyme inhibition: evidence for original antigenic sin
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/7c9329d833a84c95bbc4fca196652c5c
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Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin

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