HIV Diagnostics and Vaccines: It Takes Two to Tango.

Current serologic tests for HIV screening and confirmation of infection present challenges to the adoption of HIV vaccines. The detection of vaccine-induced HIV-1 antibodies in the absence of HIV-1 infection, referred to as vaccine-induced seropositivity/seroreactivity, confounds the interpretation of test results, causing misclassification of HIV-1 status with potential affiliated stigmatization. For HIV vaccines to be widely adopted with high community confidence and uptake, tests are needed that are agnostic to the vaccination status of tested individuals (ie, positive only for true HIV-1 infection). Successful development and deployment of such tests will require HIV vaccine developers to work in concert with diagnostic developers. Such tests will need to match today's high-performance standards (accuracy, cost-effectiveness, simplicity) for use in vaccinated and unvaccinated populations, especially in low- and middle-income countries with high HIV burden. Herein, we discuss the challenges and strategies for developing modified serologic HIV tests for concurrent deployment with HIV vaccines.

"In vitro systems to characterize the immune response to HIV-1 and HIV-1 vaccine candidates", NIAID Workshop Report, Bethesda, August 4, 2010.

Although clinical trials are the ultimate way to prove vaccine safety and efficacy, the complexity, cost and time required to develop a product to enter human trials demand a serious, long-term investment. Lack of knowledge on immune correlates of protection from HIV infections makes investments in HIV vaccine research significantly risky. Preclinical testing of HIV vaccines is routinely carried out in non-human primate models however these studies have a significant cost and their predictive value is still questionable. The potential value of screening new HIV-1 vaccine candidates on human cells and tissues via high throughput in vitro systems that allow rapid, cost-effective and accurate predictions of in vivo immune responses would be enormous. A one-day workshop was convened by Division of AIDS, National Institutes of Health on August 4, 2010 to address the benefits and challenges of assessing HIV-1 vaccine responses in alternative ways. Consideration was given to the use of various in vitro model systems, human mucosal tissue explants and humanized mouse models as ways to predict immunogenicity and efficacy of HIV-1 vaccines early in the development process, and support decisions on whether a product may be worthy of moving into non-human primates or human trials. This report summarizes the outcome of the workshop.