Preclinical efficacy studies of Influenza A haemagglutinin precursor cleavage loop peptides as a potential vaccine
Date
2011
Authors
Miller, D.
Finnie, J.
Bowden, T.
Scholz, A.
Oh, S.
Kok, T.
Burrell, C.
Trinidad, L.
Boyle, D.
Li, P.
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Journal article
Citation
Journal of General Virology, 2011; 92(5):1152-1161
Statement of Responsibility
Darren S. Miller, John Finnie, Timothy R. Bowden, Anita C. Scholz, Sawyin Oh, Tuckweng Kok, Christopher J. Burrell, Lee Trinidad, David B. Boyle and Peng Li
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Abstract
A universal influenza vaccine that does not require annual reformulation would have clear advantages over the currently approved seasonal vaccine. In this study, we combined the mucosal adjuvant alpha-galactosylceramide (αGalCer) and peptides designed across the highly conserved influenza precursor haemagglutinin (HA0) cleavage loop as a vaccine. Peptides designed across the HA0 of influenza A/H3N2 viruses, delivered to mice via the intranasal route with αGalCer as an adjuvant, provided 100 % protection following H3N2 virus challenge. Similarly, intranasal inoculation of peptides across the HA0 of influenza A/H5N1 with αGalCer completely protected mice against heterotypic challenge with H3N2 virus. Our data suggest that these peptide vaccines effectively inhibited subsequent influenza A/H3N2 virus replication. In contrast, only 20 % of mice vaccinated with αGalCer-adjuvanted peptides spanning the HA0 of H5N1 survived homologous viral challenge, possibly because the HA0 of this virus subtype is cleaved by intracellular furin-like enzymes. Results of these studies demonstrated that HA0 peptides adjuvanted with αGalCer have the potential to form the basis of a synthetic, intranasal influenza vaccine.
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© 2011 SA Pathology