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Thursday, July 3, 2014

Progress in HIV-1 Vaccine Development

Advances in HIV vaccine development have been hampered by roadblocks associated with failure to prevent infection. In recent years, a number of basic and translational science advances have shown promise in the development for an effective vaccine. In their review, Haynes and colleagues summarize these advances along with the roadblocks that still remain, as well as the most promising approaches to successful vaccine design (J Allergy Clin Immunol 2014, 134(1): 3-10). 

This year, the field of HIV-vaccine research had a major disappointment in the announcement of the lack of a vaccine efficacy seen in a DNA prime, recombinant adenovirus type 5 (rAd5) boost HIV-1 vaccine trial developed by the NIH Vaccine Research Center. The vaccine was designed to test the hypothesis that high levels of CD8+ cytotoxic T cells (CTLs) could either protect against transmission or lead to control of plasma HIV-1 viral load. The second failed trial, the Merck recombinant adenovirus type 5 trail, not only lacked vaccine efficacy, but also appeared to enhance infection in those vaccines seropositive for Ad5. Although these 2 trials were of great disappointment, they provided valuable information on the types of immune responses that are unlikely to be protective.

New advances have demonstrated a variety of promising results such as the discovery of new envelope (Env) targets of potentially protective antibodies. A recent study shows promise with the finding that CD8+ T cells are associated with control and eradication of early retrovirus infections in rhesus macaques. Another recent study shows that the development of immunogens to overcome HIV-1 T cell epitope diversity while another study identifies correlates of transmission risk in an HIV-1 efficacy trail. And finally, a recent advancement has mapped the co-evolution of HIV-1 founder Env mutants in infected individuals who develop broad neutralizing antibodies (bnAbs), thereby defining bnAb developmental pathways.

Despite these advances, the field is still years away from deployment of an effective vaccine. Moving forward in HIV-1 vaccine research requires the conversion of subdominant immune responses into dominant ones, which has yet to be accomplished by an infectious disease vaccine. HIV-1 vaccine research is breaking promising new ground in vaccinology, and success in its development will herald success for other difficult vaccines such as influenza and hepatitis C. 

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