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 poses a significant 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 represents the most important control measure to protect the population in a pandemic scenario. Thus, there is an urgent need for a highly immunogenic vaccine which efficiently targets the immune system to induce the appropriate type of immunity. The principal challenges to pandemic vaccine development are that there is limited manufacturing capacity for conventional vaccines and that clinical trials suggest that avian H5 influenza virus is poorly immunogenic. Therefore, new adjuvants will be required to obtain satisfactory responses at acceptable antigen levels. Within this project we aim to address the problems of scale-up of current influenza vaccine output, by using a novel low-cost system to produce influenza H5N1 vaccine in plants. The vaccine potency will be enhanced by exploiting a cyclic-di-nucleotide as adjuvant, which has been 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 delivery by both intranasal and parenteral routes, and its immunogenicity and protective efficacy will be evaluated by challenge with H5N1 virus in murine and ferret models. Thus, this proposal will aid the development of the most appropriate vaccine formulation to tackle this global health threat.
The project is funded by the Norwegian Research Council.
- Vaccinology - Prof. Dr. Carlos A. Guzmán