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Cross-clade protective immune responses to influenza viruses with H5N1 HA and NA elicited by an influenza virus-like particle

Bright, RA and Carter, DM and Crevar, CJ and Toapanta, FR and Steckbeck, JD and Cole, KS and Kumar, NM and Pushko, P and Smith, G and Tumpey, TM and Ross, TM (2008) Cross-clade protective immune responses to influenza viruses with H5N1 HA and NA elicited by an influenza virus-like particle. PLoS ONE, 3 (1).

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Background. Vaccination is a cost-effective counter-measure to the threat of seasonal or pandemic outbreaks of influenza. To address the need for improved influenza vaccines and alternatives to egg-based manufacturing, we have engineered an influenza virus-like particle (VLP) as a new generation of non-egg or non-mammalian cell culture-based candidate vaccine. Methodology/Principal Findings. We generated from a baculovirus expression system using insect cells, a non-infectious recombinant VLP vaccine from both influenza A H5N1 clade 1 and clade 2 isolates with pandemic potential. VLPs were administered to mice in either a one-dose or two-dose regimen and the immune responses were compared to those induced by recombinant hemagglutinin (rHA). Both humoral and cellular responses were analyzed. Mice vaccinated with VLPs were protected against challenge with lethal reassortant viruses expressing the H5N1 HA and NA, regardless if the H5N1 clade was homologous or heterologous to the vaccine. However, rHA-vaccinated mice showed considerable weight loss and death following challenge with the heterovariant clade virus. Protection against death induced by VLPs was independent of the pre-challenge HAI titer or cell-mediated responses to HA or M1 since vaccinated mice, with low to undetectable cross-clacle HAI antibodies or cellular responses to influenza antigens, were still protected from a lethal viral challenge. However, an apparent association rate of antibody binding to HA correlated with protection and was enhanced using VLPs, particularly when delivered intranasally, compared to rHA vaccines. Conclusion/Significance. This is the first report describing the use of an H5N1 VLP vaccine created from a clade 2 isolate. The results show that a non-replicating virus-like particle is effective at eliciting a broadened, cross-clade protective immune response to proteins from emerging H5N1 influenza isolates giving rise to a potential pandemic influenza vaccine candidate for humans that can be stockpiled for use in the event of an outbreak of H5N1 influenza.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Bright, RA
Carter, DM
Crevar, CJ
Toapanta, FR
Steckbeck, JD
Cole, KSstefcole@pitt.eduSTEFCOLE
Kumar, NM
Pushko, P
Smith, G
Tumpey, TM
Ross, TM
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 30 January 2008
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 3
Number: 1
DOI or Unique Handle: 10.1371/journal.pone.0001501
Refereed: Yes
PubMed ID: 18231588
Date Deposited: 18 Jul 2012 21:01
Last Modified: 02 Feb 2019 16:57


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