November 6, 2017HIV/AIDS
According to the results from an early-stage clinical trial called APPROACH, presented at the 9th International AIDS Society Conference on HIV Science in Paris, an investigational HIV vaccine regimen was well-tolerated and generated immune responses against HIV in healthy adults. The APPROACH findings, as well as results expected in late 2017 from another early-stage clinical trial called TRAVERSE, will form the basis of the decision whether to move forward with a larger trial in southern Africa to evaluate vaccine safety and efficacy among women at risk of acquiring HIV. The ongoing TRAVERSE trial is comparing Ad26-based regimens containing three mosaic antigens (trivalent) with Ad26-based regimens containing four mosaic antigens (tetravalent).
The experimental vaccine regimens evaluated in APPROACH are based on mosaic vaccines designed to induce immunological responses against a wide variety of HIV subtypes responsible for HIV infections globally. Different HIV subtypes, or clades, predominate in various geographic regions around the world. The Ad26-based mosaic vaccines were initially developed by scientists at NIAID and Janssen Pharmaceuticals. In pre-clinical studies, regimens incorporating these mosaic vaccines protected monkeys against infection with an HIV-like virus called simian human immunodeficiency virus (SHIV). The most effective prime-boost regimen reduced the risk of infection per exposure to SHIV by 94% and resulted in 66% complete protection after six exposures. The vaccine-induced immune responses that correlated with this protection were identified and characterized.
APPROACH involved nearly 400 volunteers in the United States, Rwanda, Uganda, South Africa and Thailand who were randomly assigned to receive one of seven experimental vaccine regimens or a placebo. APPROACH found that different mosaic vaccine regimens were well-tolerated and capable of generating anti-HIV immune responses in healthy, HIV-negative adults. Notably, the vaccine regimen that was most protective in pre-clinical studies in animals elicited among the greatest immune responses in the study participants. However, further research will be needed because the ability to elicit anti-HIV immune responses does not necessarily indicate that a candidate vaccine regimen can prevent HIV acquisition.
In APPROACH, study participants received four vaccinations over 48 weeks: two doses of an initial, or prime, vaccine, followed by two doses of a booster vaccine. The experimental regimens all incorporated the same vaccine components in the prime vaccination, known as Ad26.Mos.HIV. The vaccine uses a strain of common-cold virus (adenovirus serotype 26, or Ad26), engineered so that it does not cause illness, as a vector to deliver three mosaic antigens created from genes from many HIV variants. The booster vaccination included various combinations of the Ad26.Mos.HIV components or a different mosaic component, called MVA-Mosaic, and/or two different doses of clade C HIV gp140 envelope protein containing an aluminum adjuvant to boost immune responses. Following the third vaccination, most APPROACH participants had developed antibody and cellular immune responses against HIV. The different boost vaccines altered the magnitude and character of these immune responses, with the regimen that showed greatest protection in monkey studies also eliciting among the greatest immune responses in humans. The anti-HIV immune responses increased after the fourth vaccination.