To achieve (i) effective protective immunity, (ii) a high population response, (iii) prolonged duration of immunity, and (iv) high level of safety, novel vaccines should combine the efficacy of live (attenuated) vaccines and the safety of subunit vaccines. A vaccine resulting in antigen presentation which mimics that during natural infection by the cognate pathogen would appear have the highest probability of success.
The present proposal presents a novel strategy of vaccine design to meet the above goals. Vaccine vectors are described which are based on a self-replicating, suicidal, recombinant RNA, originating from Semliki Forest virus (SFV). In this system, genes encoding relevant antigens are cloned into vectors which upon vaccination will transiently express the antigen within the cells of the host. Preliminary studies have already shown that this strategy results in a strong induction of the humoral and cellular arms of the immune system with sustained immunologic memory. Extensive in-depth studies are described to further characterize the immune responses for optimal design of individual vaccines. These studies will, among others, include the co-expression of antigen and cytokines and/or co-stimulatory factors. The present proposal further describes development of the SFV system to allow efficient delivery of vaccines as infectious, suicidal virus particles, as naked nucleic acids (NA) or as NA-lipid complexes. A number of vaccine candidates will be employed to test the functionality and efficacy of the SFV system as a transdisease vaccine strategy. Diverse applications will cover vaccines directed against influenza virus, flavivirus, lentivirus and papilloma virus infection as well as cancer.
The SFV system is by design quite safe, but studies will be conducted to further address biosafety, in preparation for human trials. Work is also described for the design of scale up production of vaccine preparations. Finally, industrial links are already in place for rapid exploitation of results stemming from this Project.
The tasks outlined in this Project proposal will comply with most, if not all, objectives set forth in the EC Biotechnology Workprogramme.
Funding SchemeCSC - Cost-sharing contracts
EN6 3QG Potters Bar
9713 AV Groningen