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PMID: 20352112 Published · epublish English Comparative Study Journal Article Research Support, N.I.H., Extramural

Comparative efficacy of hemagglutinin, nucleoprotein, and matrix 2 protein gene-based vaccination against H5N1 influenza in mouse and ferret.

PloS one ·Vol. 5 ·No. 3 ·2010-03-23 ·Pages e9812

Rao SS, Kong WP, Wei CJ, Van Hoeven N, Gorres JP, Nason M, Andersen H, Tumpey TM, Nabel GJ

Abstract

Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge.

MeSH Terms
Adenoviridae/genetics Animals Female Ferrets Hemagglutinin Glycoproteins, Influenza Virus/chemistry Humans Influenza A Virus, H5N1 Subtype/metabolism Influenza Vaccines/chemistry Male Mice Mice, Inbred BALB C Neutralization Tests Nucleoproteins/chemistry Plasmids/metabolism Viral Matrix Proteins/chemistry
Chemicals
Hemagglutinin Glycoproteins, Influenza Virus Influenza Vaccines M2 protein, Influenza A virus Nucleoproteins Viral Matrix Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Rao Srinivas S
Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, Maryland, United States of America.
Kong Wing-Pui
Wei Chih-Jen
Van Hoeven Neal
Gorres J Patrick
Nason Martha
Andersen Hanne
Tumpey Terrence M
Nabel Gary J
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0009812
Published
2010-03-23
Epub
2010-00-23
Pages
e9812
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2843722
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0009812 PMC Full Text View journal details
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