Viral & host immunomodulators in improved Fowlpox virus recombinant vector vaccines for use in poultry against highly pathogenic avian influenza H5N1.

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Recombinant Fowlpox viruses (rFWPV) are playing an important role in China in attempts to control high pathogenicity avian influenza H5N1 virus in poultry. rFWPV expressing H5 were first employed in Mexico during the campaign to control high pathogenicity H5N2, with almost a billion doses used. New recombinants, derived in China to express H5 and N1 homologous for the current panzootic, are being used in a massive vaccination campaign (some 5 billion poultry). Although rFWPV are reported to be effective in controlling disease, it is not clear how effective they are at inducing cellular immunity and controlling spread. It is likely that spread will be most effectively controlled by induction of cellular as well as improved humoral/mucosal immunity. We intend to investigate methods of (a) improving induction of humoral/mucosal immunity and (b) driving cell-mediated responses after vaccination with rFWPV. Cell-mediated immunity will probably require expression of internal and non-structural proteins (nucleoprotein will not be included as its absence is important in differential diagnosis). Coexpression of host-derived cytokines by rFWPV has been shown to affect the humoral/cellular balance of the immune response, improving vaccine efficacy in certain cases. We therefore aim to generate a spectrum of responses for each arm of the immune system by coexpression of a variety of host cytokines (and one viral cytokine) so that we can optimise the desired response. Significant improvement in efficacy may alternatively be achieved by deletion of FWPV-encoded immunomodulators that bind host cytokines, without the safety concerns attracted by expression of host cytokines. We will therefore investigate the effect of deleting two such viral immunomodulators from the rFWPV vectors. The nature of the humoral and cellular immune responses induced by the various modified recombinants will be assayed in vivo, both before and after challenge with highly pathogenic H5N1.