The NIH has released the findings of the first of 2 early-stage clinical trials on assessing the safety and effectiveness of HIV candidate vaccinations that support additional development of vaccines.
The National Institutes of Health (NIH) released the findings of the first of 2 early-stage clinical trials on assessing the safety and effectiveness of HIV candidate vaccinations that support additional development of vaccines. Results from APPROACH, the first clinical trial, indicated that experimental vaccine regimens were well-tolerated and produced immune system defenses against HIV in HIV-negative adults. The results were presented July 24 at the 9th International AIDS Society Conference on HIV Science in Paris.
Data from the other trial, TRAVERSE, are expected later this year and a larger trial could begin testing vaccination regimens in 2,600 HIV-negative women at high risk for the virus in southern Africa as early as late 2017, according to the researchers.
APPROACH participants included nearly 400 individuals from the United States, Rwanda, Uganda, South Africa, and Thailand. An important part of the preclinical process, funded by the National Institute of Allergy and Infectious Diseases (NIAD), included identifying various subtypes connected to HIV infections in different areas of the world. Using this information, Janssen manufactured and developed “mosaic” vaccines that were constructed to active the immune system’s defenses against varieties of subtypes. The news release also noted that “Together with other partners, NIAID supported the APPROACH trial, which is sponsored by Janssen Vaccines & Prevention B.V., part of the Janssen Pharmaceutical Companies of Johnson & Johnson.”
Because the study was randomized, each patient was placed in 1 of 7 experimental groups or the placebo group. Each volunteer received 4 vaccinations over the course of 48 weeks; 2 prime vaccines and 2 booster vaccines. Ad26.Mos.HIV, the prime vaccination, was incorporated in all 7 experimental groups. The vaccination used a modified version of the common-cold virus to distribute 3 mosaic antigens developed from genes of various HIV variants.
The booster vaccinations differed from group to group. The booster either consisted of “various combinations of the Ad26Mos.HIV components or a different mosaic component, called MVA-Mosaic, and/or 2 different doses of clade C HIV gp140 envelope protein containing an aluminum adjuvant to boost immune responses.”
Dan H. Baluch, MD, PhD, who received an NIAID grant, and Janssen collaborated on designing the Ad26-based mosaic vaccines. The vaccines were tested in preclinical studies among animals, and the results indicated the most effective regimen in a study with monkeys could diminish the risk of infection per exposure by 94% and 66% of full protection occurred after six exposures.
In the APPROACH study, after the third vaccination, most participants showed signs of antibodies and immune responses against HIV. The level of responses varied based off the different experimental groups, but the most effective regimen in humans was the most effective regimen in monkeys, as well. The immune responses continued to grow following the fourth vaccination.
The researchers found that more evaluation of this approach would use a regimen comprising 2 Ad26 mosaic primes and 2 boosts with Ad26 mosaic and clade C gp140, according to the NIH release. The ongoing TRAVERSE trial is comparing Ad26-based regimens that have 3 mosaic antigens (trivalent) with Ad26-based regimens that contain 4 mosaic antigens (tetravalent).