Giuseppe
Emeritus
J Virol. 2008 Sep 10. [Epub ahead of print]
Membrane-anchored Flagellin Incorporation into Influenza VLPs Enhances the Breadth of Immune Responses.
Wang BZ, Quan FS, Kang SM, Bozja J, Skountzou I, Compans RW. - Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322.
We have designed a membrane-anchored form of the Toll-like receptor 5 (TLR-5) ligand flagellin, the major proinflammatory determinant of enteropathogenic Salmonella, which was found to be glycosylated and expressed on cell surfaces.
A chimeric influenza virus-like particle (cVLP) vaccine candidate containing A/PR8/34 (H1N1) hemagglutinin (HA), matrix protein (M1) and the modified flagellin as a molecular adjuvant was produced.
The immunogenicity, including the serum antibody levels and cellular immune responses, and protective efficacy against homologous and heterologous live virus challenge of the resulting VLPs were tested after intramuscular (i.m.) administration in a mouse model.
The results demonstrated that flagellin-containing VLPs elicited higher specific IgG responses than standard HA and M1 VLPs, indicating the adjuvant effect of flagellin.
Enhanced IgG2a and IgG2b, but not IgG1 responses, were observed with flagellin-containing VLPs, illuminating the activation of Th1 class immunity.
The adjuvant effects of flagellin were also reflected by enhanced specific cellular responses, revealed by the secretion of cytokines by freshly isolated splenocyte cultures when stimulated with pools of major histocompatibility complex (MHC) class I or II peptides.
When immunized mice were challenged with homologous live PR8 virus, complete protection was observed in both the standard and chimeric VLP groups.
However when a heterosubtypic virus A/Philippines (H3N2) was used for challenge, all of the standard VLP group lost at least 25% of body weight, reaching the experimental endpoint.
In contrast, for the chimeric VLP group, 67% of mice survived the challenge infection.
These results reveal that chimeric VLPs designed by incorporating flagellin as a membrane-anchored adjuvant induce enhanced cross-protective heterosubtypic immune responses.
They also indicate that such chimeric VLP vaccines are a promising new approach for protection against pandemic influenza viruses.
PMID: 18786995 [PubMed - as supplied by publisher
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Membrane-anchored Flagellin Incorporation into Influenza VLPs Enhances the Breadth of Immune Responses.
Wang BZ, Quan FS, Kang SM, Bozja J, Skountzou I, Compans RW. - Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322.
We have designed a membrane-anchored form of the Toll-like receptor 5 (TLR-5) ligand flagellin, the major proinflammatory determinant of enteropathogenic Salmonella, which was found to be glycosylated and expressed on cell surfaces.
A chimeric influenza virus-like particle (cVLP) vaccine candidate containing A/PR8/34 (H1N1) hemagglutinin (HA), matrix protein (M1) and the modified flagellin as a molecular adjuvant was produced.
The immunogenicity, including the serum antibody levels and cellular immune responses, and protective efficacy against homologous and heterologous live virus challenge of the resulting VLPs were tested after intramuscular (i.m.) administration in a mouse model.
The results demonstrated that flagellin-containing VLPs elicited higher specific IgG responses than standard HA and M1 VLPs, indicating the adjuvant effect of flagellin.
Enhanced IgG2a and IgG2b, but not IgG1 responses, were observed with flagellin-containing VLPs, illuminating the activation of Th1 class immunity.
The adjuvant effects of flagellin were also reflected by enhanced specific cellular responses, revealed by the secretion of cytokines by freshly isolated splenocyte cultures when stimulated with pools of major histocompatibility complex (MHC) class I or II peptides.
When immunized mice were challenged with homologous live PR8 virus, complete protection was observed in both the standard and chimeric VLP groups.
However when a heterosubtypic virus A/Philippines (H3N2) was used for challenge, all of the standard VLP group lost at least 25% of body weight, reaching the experimental endpoint.
In contrast, for the chimeric VLP group, 67% of mice survived the challenge infection.
These results reveal that chimeric VLPs designed by incorporating flagellin as a membrane-anchored adjuvant induce enhanced cross-protective heterosubtypic immune responses.
They also indicate that such chimeric VLP vaccines are a promising new approach for protection against pandemic influenza viruses.
PMID: 18786995 [PubMed - as supplied by publisher
-
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