Date Published: August 12, 2008
Publisher: Public Library of Science
Author(s): Cecilia Morgan, Marta Marthas, Christopher Miller, Ann Duerr, Cecilia Cheng-Mayer, Ronald Desrosiers, Jorge Flores, Nancy Haigwood, Shiu-Lok Hu, R. Paul Johnson, Jeffrey Lifson, David Montefiori, John Moore, Marjorie Robert-Guroff, Harriet Robinson, Steven Self, Lawrence Corey
Abstract: Cecilia Morgan and colleagues outline a two-stage nonhuman primate screening strategy for T cell-based HIV-1 vaccines.
Partial Text: In April 2006, the National Institute of Allergy and Infectious Disease (NIAID)-funded HIV Vaccine Trials Network and the NIAID Division of AIDS sponsored a workshop at which nonhuman primate (NHP) researchers and clinical trial scientists with HIV vaccine research expertise discussed how to more effectively use NHPs for evaluating HIV-1 vaccine candidates. This workshop precipitated a broad discussion on what types of NHP studies should be targeted in the critical preclinical pathway for HIV-1 vaccine candidates, especially those designed to elicit HIV-1-specific T cell responses. This paper describes the two-stage NHP screening strategy for T cell–based HIV-1 vaccines that emerged from discussions among the authors during the past year and a half. While conceived prior to the recent release of results for the phase IIB trial (STEP Study) of the Merck replication-incompetent adenovirus serotype 5 (Ad5)-HIV gag/pol/nef vaccine, we think the approach outlined below will be particularly useful for preclinical evaluation of vaccine candidates in the current vaccine pipeline for two reasons. First, the proposed strategy will eliminate suboptimal vaccine candidates early in the testing process (i.e., before initiation of phase I clinical trials). Second, the strategy would provide comparative immune response data in NHPs and humans for each promising HIV-1 vaccine product, information that could help the design of future vaccine candidates.
There is a clear consensus that we must expedite the process of moving HIV-1 vaccine candidates from preclinical to clinical studies, using the most scientifically rigorous, efficient, and cost-effective strategies available. Furthermore, stringent criteria are needed to identify the HIV-1 vaccine candidates most likely to lead to a safe and effective vaccine product. To accomplish these shared goals, we strongly recommend identifying and implementing a strategy that places standardized, coordinated NHP studies in a central role in the preclinical evaluation of HIV-1 vaccines. Moreover, we recommend that HIV-1 vaccine candidates now advancing in the clinical pipeline also be evaluated by this NHP strategy to provide essential comparative data; determining which NHP studies should be conducted for each product currently in clinical trials should be done on a case-by-case basis. Our consensus proposal is a two-pronged strategy for evaluation of candidate vaccines in NHPs, using biologically based, clinically relevant endpoints to define go/no-go decision points prior to entry into phase I clinical trials (Figure 2).