title: Preclinical efficacy studies of influenza A haemagglutinin precursor cleavage loop peptides as a potential vaccine.
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 (HA(0)) cleavage loop as a vaccine. Peptides designed across the HA(0) 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 HA(0) 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 HA(0) of H5N1 survived homologous viral challenge, possibly because the HA(0) of this virus subtype is cleaved by intracellular furin-like enzymes. Results of these studies demonstrated that HA(0) peptides adjuvanted with αGalCer have the potential to form the basis of a synthetic, intranasal influenza vaccine.
authors.affiliation: Microbiology-IMVS, SA Pathology, Frome Road, Adelaide, SA 5000, Australia.
authors.forename: Darren S
authors.initials: DS
authors.lastname: Miller
authors.affiliation: Veterinary Services, SA Pathology, School of Veterinary Science, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Finnie
authors.affiliation: CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, VIC 3220, Australia.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Bowden
authors.affiliation: University of South Australia, Adelaide, SA 5005, Australia.
authors.forename: Anita C
authors.initials: AC
authors.lastname: Scholz
authors.affiliation: Microbiology-IMVS, SA Pathology, Frome Road, Adelaide, SA 5000, Australia.
authors.forename: Sawyin
authors.initials: S
authors.lastname: Oh
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005, Australia.|Microbiology-IMVS, SA Pathology, Frome Road, Adelaide, SA 5000, Australia.
authors.forename: Tuckweng
authors.initials: T
authors.lastname: Kok
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005, Australia.|Microbiology-IMVS, SA Pathology, Frome Road, Adelaide, SA 5000, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Burrell
authors.affiliation: CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, VIC 3220, Australia.
authors.forename: Lee
authors.initials: L
authors.lastname: Trinidad
authors.affiliation: CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, VIC 3220, Australia.
authors.forename: David B
authors.initials: DB
authors.lastname: Boyle
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005, Australia.|Microbiology-IMVS, SA Pathology, Frome Road, Adelaide, SA 5000, Australia.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001835:Body Weight; D056738:Cross Protection; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000276:immunology*; D006651:Histocytochemistry; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008853:Microscopy; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000517:prevention & control; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D005699:Galactosylceramides; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011498:Protein Precursors; D022223:Vaccines, Subunit