Development of Novel Molecular Adjuvants for Genetic Vaccination

Vaccination represents one of the most effective methods for combating infectious diseases. However, there are a number of common and serious diseases for which, to date, no vaccine has been successfully developed. Many of these infectious diseases are caused by intracellular pathogens like human immunodeficiency virus, Mycobacterium tuberculosis (Mtb), Plasmodium falciparum, and Chlamydia trachomatis (Ct). It is known that type 1 cell-based immunity (CMI) is required for immune protection against these intracellular pathogens. While genetic vaccines such as vaccines based on one of the common "cold" viruses, adenoviruses, are very promising for stimulating CMI, in most cases single dose delivery of adenovirus-based vaccines is not able to stimulate a sufficient robust or sustainable protective immunity. One of the potential obstacles is the concurrent production of suppressive type of immunity by vaccination. This proposed study will develop a novel type of vaccine adjuvant that prevents the induction of such negative immunity by manipulating the cell signalling inside of a critical immune subset of cells called dentritic cells whereby to enhance the efficacy of these viral vector-based vaccines. Results obtained from this study will contribute to the development of the next generation of genetic vaccines against many infections.