Elicitation of protective immune responses using a bivalent H5N1 VLP vaccine

BACKGROUND: Currently licensed human vaccines are subtype-specific and do not protect against pandemic H5N1 viruses. Previously, our group has reported on the construction of an influenza virus-like particle (VLP) as a new generation candidate vaccine. A mixture of influenza H5N1 VLPs representing clade 1 and 2 viruses were examined for the ability to elicit protective immunity against isolates from various clades and subclades of H5N1. RESULTS: Mice were vaccinated intramuscularly with each VLP individually, the mixture of VLPs, a mixture of purified recombinant hemagglutinin (rHA), or mock vaccinated. Elicited antibodies were assayed for the hemagglutination-inhibition (HAI) activity against clades 1 and clade 2 isolates. Mice vaccinated with each VLP individually or in a mixture had robust HAI responses against homologous viruses and HAI responses against the clade 2.3 virus, Anh/05. However, these vaccines did not induce an HAI response against the clade 2.2 virus, WS/05. Interestingly, clade 2 VLP vaccinated mice were protected against both clade 1 and 2 H5/PR8 viruses, but clade 1 VLP vaccinated mice were only protected against the clade 1 virus. Mice vaccinated with a mixture of VLPs were protected against both clade 1 and 2 viruses. In contrast, mice vaccinated with a mixture of rHA survived challenge, but lost ~15% of original weight by days 5–7 post-challenge. CONCLUSION: These results demonstrate that a multivalent influenza VLP vaccine representing different genetic clades is a promising strategy to elicit protective immunity against isolates from emerging clades and subclades of H5N1.