Studies carried out previously in our lab that characterized the immune response following HIV infection, enable the design of new vaccines. Over the last 10 years, our lab has developed a platform that has also allowed us to initiate and carry out clinical studies to test these new vaccines.
Many challenges remain in developing safer and more effective vaccines against complex diseases such as tuberculosis (TB) and HIV. It has long been recognized that most antigens require the addition of an “adjuvant” to trigger the innate immune system and boost a specific adaptive immune response, with aluminum-based adjuvants being the most commonly used in most present vaccines. Generation of novel adjuvant formulations, tailored to induce defined cell mediated immune responses effective against TB and HIV are crucial in the development of effective vaccines. Our laboratory aims at developing immunological adjuvant that act to accelerate, prolong and enhance the antigen specific immune response against TB and HIV when added to recombinant viral vectors.
Replication-deficient adenoviruses vectors are attractive because of their ability to infect both resting and dividing cells, their capacity to accommodate large transgenes, the low frequency of integration into the host genome, and the relative ease of production of recombinant virus in the laboratory.
In 2007, a HIV-vaccine study using Ad5 as delivery vector was prematurely interrupted due to the lack of efficacy. Interestingly, uncircumcised vaccinees displaying high neutralizing antibody (Nab) titers to Ad5 had a higher rate of HIV infection as compared to vaccinees with no or low Ad5 specific Nabs. In order to understand the capacity of the vaccine to elicit specific anti-viral responses, we also need to understand the role of the delivery vector and its own ability to activate the immune system.