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Vaccination with Recombinant Parainfluenza Virus 5 Expressing Neuraminidase Protects against Homologous and Heterologous Influenza Virus Challenge.

作者信息

Mooney Alaina J, Gabbard Jon D, Li Zhuo, Dlugolenski Daniel A, Johnson Scott K, Tripp Ralph A, He Biao, Tompkins S Mark

机构信息

Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.

Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA

出版信息

J Virol. 2017 Nov 14;91(23). doi: 10.1128/JVI.01579-17. Print 2017 Dec 1.


DOI:10.1128/JVI.01579-17
PMID:28931689
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5686712/
Abstract

Seasonal human influenza virus continues to cause morbidity and mortality annually, and highly pathogenic avian influenza (HPAI) viruses along with other emerging influenza viruses continue to pose pandemic threats. Vaccination is considered the most effective measure for controlling influenza; however, current strategies rely on a precise vaccine match with currently circulating virus strains for efficacy, requiring constant surveillance and regular development of matched vaccines. Current vaccines focus on eliciting specific antibody responses against the hemagglutinin (HA) surface glycoprotein; however, the diversity of HAs across species and antigenic drift of circulating strains enable the evasion of virus-inhibiting antibody responses, resulting in vaccine failure. The neuraminidase (NA) surface glycoprotein, while diverse, has a conserved enzymatic site and presents an appealing target for priming broadly effective antibody responses. Here we show that vaccination with parainfluenza virus 5 (PIV5), a promising live viral vector expressing NA from avian (H5N1) or pandemic (H1N1) influenza virus, elicited NA-specific antibody and T cell responses, which conferred protection against homologous and heterologous influenza virus challenges. Vaccination with PIV5-N1 NA provided cross-protection against challenge with a heterosubtypic (H3N2) virus. Experiments using antibody transfer indicate that antibodies to NA have an important role in protection. These findings indicate that PIV5 expressing NA may be effective as a broadly protective vaccine against seasonal influenza and emerging pandemic threats. Seasonal influenza viruses cause considerable morbidity and mortality annually, while emerging viruses pose potential pandemic threats. Currently licensed influenza virus vaccines rely on the antigenic match of hemagglutinin (HA) for vaccine strain selection, and most vaccines rely on HA inhibition titers to determine efficacy, despite the growing awareness of the contribution of neuraminidase (NA) to influenza virus vaccine efficacy. Although NA is immunologically subdominant to HA, and clinical studies have shown variable NA responses to vaccination, in this study, we show that vaccination with a parainfluenza virus 5 recombinant vaccine candidate expressing NA (PIV5-NA) from a pandemic influenza (pdmH1N1) virus or highly pathogenic avian influenza (H5N1) virus elicits robust, cross-reactive protection from influenza virus infection in two animal models. New vaccination strategies incorporating NA, including PIV5-NA, could improve seasonal influenza virus vaccine efficacy and provide protection against emerging influenza viruses.

摘要

相似文献

[1]
Vaccination with Recombinant Parainfluenza Virus 5 Expressing Neuraminidase Protects against Homologous and Heterologous Influenza Virus Challenge.

J Virol. 2017-11-14

[2]
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[3]
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[5]
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[6]
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[8]
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本文引用的文献

[1]
Influenza Neuraminidase Subtype N1: Immunobiological Properties and Functional Assays for Specific Antibody Response.

PLoS One. 2016-4-7

[2]
Mucosal administration of raccoonpox virus expressing highly pathogenic avian H5N1 influenza neuraminidase is highly protective against H5N1 and seasonal influenza virus challenge.

Vaccine. 2015-9-22

[3]
Persistence of Antibodies to Influenza Hemagglutinin and Neuraminidase Following One or Two Years of Influenza Vaccination.

J Infect Dis. 2015-12-15

[4]
Cross-Reactive Neuraminidase-Inhibiting Antibodies Elicited by Immunization with Recombinant Neuraminidase Proteins of H5N1 and Pandemic H1N1 Influenza A Viruses.

J Virol. 2015-7

[5]
Antibody to Influenza Virus Neuraminidase: An Independent Correlate of Protection.

J Infect Dis. 2015-10-15

[6]
Vaccination with adjuvanted recombinant neuraminidase induces broad heterologous, but not heterosubtypic, cross-protection against influenza virus infection in mice.

mBio. 2015-3-10

[7]
Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP) -- United States, 2014-15 influenza season.

MMWR Morb Mortal Wkly Rep. 2014-8-15

[8]
In the shadow of hemagglutinin: a growing interest in influenza viral neuraminidase and its role as a vaccine antigen.

Viruses. 2014-6-23

[9]
Stability of neuraminidase in inactivated influenza vaccines.

Vaccine. 2014-3-6

[10]
T-cell immunity to influenza A viruses.

Crit Rev Immunol. 2014

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