Preclinical efficacy studies of Influenza A haemagglutinin precursor cleavage loop peptides as a potential vaccine

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dc.contributor.authorMiller, D.
dc.contributor.authorFinnie, J.
dc.contributor.authorBowden, T.
dc.contributor.authorScholz, A.
dc.contributor.authorOh, S.
dc.contributor.authorKok, T.
dc.contributor.authorBurrell, C.
dc.contributor.authorTrinidad, L.
dc.contributor.authorBoyle, D.
dc.contributor.authorLi, P.
dc.date.issued2011
dc.description.abstractA 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.
dc.description.statementofresponsibilityDarren 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
dc.identifier.citationJournal of General Virology, 2011; 92(5):1152-1161
dc.identifier.doi10.1099/vir.0.028985-0
dc.identifier.issn0022-1317
dc.identifier.issn1465-2099
dc.identifier.orcidFinnie, J. [0000-0003-2277-1693]
dc.identifier.orcidBurrell, C. [0000-0002-4020-349X]
dc.identifier.urihttp://hdl.handle.net/2440/66553
dc.language.isoen
dc.publisherSoc General Microbiology
dc.rights© 2011 SA Pathology
dc.source.urihttps://doi.org/10.1099/vir.0.028985-0
dc.subjectLung
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectMice
dc.subjectOrthomyxoviridae Infections
dc.subjectBody Weight
dc.subjectGalactosylceramides
dc.subjectProtein Precursors
dc.subjectHemagglutinin Glycoproteins, Influenza Virus
dc.subjectVaccines, Subunit
dc.subjectInfluenza Vaccines
dc.subjectAdjuvants, Immunologic
dc.subjectMicroscopy
dc.subjectHistocytochemistry
dc.subjectViral Load
dc.subjectFemale
dc.subjectInfluenza A Virus, H3N2 Subtype
dc.subjectInfluenza A Virus, H5N1 Subtype
dc.subjectCross Protection
dc.titlePreclinical efficacy studies of Influenza A haemagglutinin precursor cleavage loop peptides as a potential vaccine
dc.typeJournal article
pubs.publication-statusPublished

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