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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 (HA) cleavage loop as a vaccine. Peptides designed across the HA 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 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 of H5N1 survived homologous viral challenge, possibly because the HA of this virus subtype is cleaved by intracellular furin-like enzymes. Results of these studies demonstrated that HA peptides adjuvanted with αGalCer have the potential to form the basis of a synthetic, intranasal influenza vaccine.

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2011-05-01
2020-01-29
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vol. , part 5, pp. 1152 - 1161

BALB/c mice were vaccinated with 10 or 50 µg of H3 HA

Passive transfer of antisera from H3 HA peptide immunized mice to naive mice and challenge with H3N2 X31 virus

(a) Day 3 p.i. Twenty BALB/c mice were vaccinated with either H3 HA peptides and 0.3 µg αGalCer or saline control and then challenged with 6 MID50 H3N2 X31 [Single PDF file](1096 KB)



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