The Immunogenicity and Protective Efficacy of Plant-Derived Influenza H5N1 Vaccine in Preclinical Models.

Influenza epidemics remain a burden to both human health and national economies, and parenteral influenza vaccines are the most effective prophylactic measure. The global spread of highly pathogenic avian influenza H5 virus, causing the largest and most s evere avian outbreaks in history, poses a risk to human health. The virus has crossed the species barrier into man infecting over 300 people and could potentially give rise to a pandemic at any time. Influenza vaccination will be an important control meas ure in protecting the population in a pandemic scenario and there is an urgent need for a highly immunogenic vaccine which efficiently targets the immune system to induce the appropriate immunity. The principal challenges to pandemic vaccine development a re that there is limited manufacturing capacity for conventional vaccines and that to date clinical trials have shown that avian H5 influenza virus is poorly immunogenic. Therefore, new adjuvants will be required to obtain satisfactory responses at accept able antigen levels This proposal aims to address the problems of scale-up of current influenza vaccine output, by using a low cost new transient plant production system to produce influenza H5N1 vaccine. The vaccine potency will be enhanced by the adjuv ant cgiGMP shown to direct the immune response towards a Th1/Th2 profile, avoiding the Th2-skewing when using non-living vaccine material. The vaccine will be formulated for both intranasal or parenteral delivery and its immunogenicity and protective effi cacy evaluated by challenge with H5N1 virus in murine and ferret models. Thus, this proposal will aid in the development of the most appropriate vaccine formulation and define its optimal use helping in the urgent need to prepare for this global health th reat.