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Preclinical efficacy studies of influenza A haemagglutinin precursor loop peptides as a potential vaccine.

tetano

Editor, Senior Moderator
Published online ahead of print on 2 February 2011 as doi:10.1099/vir.0.028985-0
J Gen Virol (2011), DOI 10.1099/vir.0.028985-0
? 2011 Society for General MicrobiologyPreclinical efficacy studies of influenza A haemagglutinin precursor loop peptides as a potential vaccine.
Darren Miller1, John Finnie1, Timothy Bowden2, Anita Scholz1, Sawyin Oh1, Tuckweng Kok1,4, Christopher Burrell3, Lee Trinidad2, David Boyle2 and Peng Li1

1 SA Pathology-IMVS;
2 CSIRO;
3 University of Adelaide

4 E-mail: tuckweng.kok@health.sa.gov.au

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 ({alpha}GalCer) 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 {alpha}GalCer as adjuvant, provided 100% protection following H3N2 virus challenge. Similarly, intranasal inoculation of peptides across the HA0 of Influenza A/H5N1 with {alpha}GalCer 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 {alpha}GalCer-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 {alpha}GalCer have the potential to form the basis of a synthetic, intranasal, influenza vaccine.

Received 17 November 2010; accepted 28 January 2011.

http://vir.sgmjournals.org/cgi/content/abstract/vir.0.028985-0v1
 
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