A major roadblock in designing effective vaccines for some diseases is the inability of some formulations to reliably induce potent cell-mediated immunity. Viral vectored vaccines appear to be a promising means of overcoming this problem. These vectored vaccines place genetic material from the disease into a harmless virus, which presents the material to the immune system to elicit specific immune responses. For these vaccines to be effective, however, they must stimulate greater immune responses than achieved so far.
 
Dr. Hill and his colleagues are exploring a novel approach to enhancing the ability of plasmid DNA, pox, or adenoviral vectored vaccines to stimulate strong immune responses. Building on recent advances in understanding of pattern recognition molecules as well as intracellular signaling pathways, investigators are working to add intracellular adjuvants (molecular signals that have the potential to enhance immunogenicity) to the vaccine vectors. Also being explored is the effect of adding molecules designed to inhibit regulatory pathways that may be limiting protective immune response. The team is focusing on improving vectors for vaccines against malaria, HIV, and tuberculosis.

Dr. Hill and his colleagues are modifying DNA, Modified Vaccinia Virus Ankara (MVA), and adenovirus vectors by the addition – and in the case of MVA, the deletion – of potential immunomodulatory genes. The project team is collaborating with Okairos AG to produce a series simian adenovirus vectors. They will conduct immunogenicity experiments in non-human primates, which if successful will lead to selection of candidates for a human malaria clinical trial. Partners at Cambridge Biostability Ltd. are working to develop thermostable formulations of live viral vectors that would enhance vaccine deployment in developing countries.