Elicitation of protective immune responses using a bivalent H5N1 VLP vaccine

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Abstract
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. 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. 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.