The HIV Vaccine Pipeline
José Esparza
from: AIDS Vaccine Development: Challenges and Opportunities (Edited by: Wayne Koff, Patricia Kahn and Ian D. Gust). Caister Academic Press, U.K. (2007)
Abstract
Since the first human trial of an HIV candidate vaccine was conducted in 1987, the HIV vaccine pipeline has experienced an important evolution. The first wave of candidate vaccines, based on the concept that neutralizing antibodies were capable of conferring protection against HIV/AIDS, lead to the development of the first generation of envelope vaccines, mostly based on gp120. The second wave was guided by the paradigm that cytotoxic T-cells (CTL) were responsible for protection, and candidate vaccines were developed based on live recombinant viral vectors and naked DNA. The third wave is just starting, with the recognition that a highly effective preventive vaccine may have to induce both broadly reactive antibodies capable of neutralizing primary isolates of HIV, as well as long lasting cross-reactive CTL. Different candidate vaccines and combinations are now in the pre-clinical pipeline, and some of them are already moving to clinical trials. Novel approaches, such as the use of structural biology, or a more careful consideration of HLA-escape epitopes, promise a new era of more rational vaccine design. With the availability of larger numbers of candidate vaccines, a more systematic approach to expand and explore the pipeline is needed. This requires the standardization of reagents, techniques and criteria to move candidate vaccines through the pipeline in a comparative fashion, including immunogenicity assays and animal protection experiments. It is also increasingly recognized that carefully designed efficacy trials (Phase IIb or Phase III) are essential for the identification of immune correlates of protection, information that would accelerate the future development or improvement of HIV vaccines read more ...
