PROGRESS TOWARD DEVELOPMENT OF A VACCINE TO PREVENT AIDS

Since the first reports that a whole-killed SIV vaccine protected monkeys from SIV infection, research on the design and development of candidate prophylactic vaccines to prevent the acquired immunodeficiency syndrome (AIDS) has escalated rapidly. Over 20 candidates have undergone preclinical evaluation for safety and immunogenicity. A few have demonstrated the ability to protect animals from intravenous and/or mucosal challenge with homologous HIV or SIV given shortly after immunization was completed. Several vaccine candidates have entered phase 1 clinical testing in uninfected volunteers and two candidates entered phase 2 testing in larger numbers of individuals, including those at higher risk for HIV infection. In addition, the complex process of preparing for phase 3 trials has begun in the United States and other countries. The purpose of this review is to summarize the status of HIV vaccine development and to highlight critical questions that need to be addressed. Current challenges include increasing the magnitude, duration, and breadth of the immune response to candidate vaccines in humans, consistently eliciting CD8+ cytotoxic T cells in humans, and using animal models and/or in vitro approaches to determine if the immune responses to candidate vaccines in human volunteers might be protective against HIV strains that individuals at risk are likely to encounter.