An experimental HIV-1 vaccine regimen, mosaic adenovirus serotype 26 (Ad26) was well-tolerated and produced immune responses against HIV in humans and rhesus monkeys, according to findings from a phase 1/2a clinical trial published
in the Lancet
In the APPROACH trial, 393 individuals with a low risk of HIV were recruited to receive either 1 of 7 vaccine combinations or a placebo; they were given 4 vaccinations over 48 weeks. To stimulate an initial immune response, each participant received an injection of Ad26.Mos.HIV at the advent of the study and 12 weeks later. Two additional vaccinations were given at week 24 and week 48 using combinations of Ad26.Mos.HIV or a different vaccine component referred to as modified Vaccinia Ankara (MVA) with or without 2 different doses of clade C HIV gp140 protein. The researchers found that all vaccine regimens were well-tolerated and were able to induce anti-HIV immune responses in healthy individuals. Similar systemic reactions were reported in all groups included in the trial.
In a parallel study, the efficacy of the candidate was assessed in 72 rhesus monkeys with simian-human immunodeficiency virus (SHIV) a virus similar to HIV that affects monkeys. The Ad26/Ad26 plus gp140 vaccine candidate induced the greatest immune responses in humans and provided complete protection in two-thirds of the monkeys after six challenges.
"These results represent an important milestone,” said Dan Barouch, MD, professor of medicine at Harvard Medical School, director, Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, and leader of the study in a statement
. “This study demonstrates that the mosaic Ad26 prime, Ad26 plus gp140 boost HIV vaccine candidate induced robust immune responses in humans and monkeys with comparable magnitude, kinetics, phenotype, and durability and also provided 67% protection against viral challenge in monkeys.”
Primary endpoints of the APPROACH trial were safety and tolerability of the vaccine regimens and HIV-1 envelope specific binding antibody responses at week 28. Safety and immunogenicity were also assessed at week 52.
The regimens used in this study are based on unique “mosaic” vaccines that utilize pieces of different HIV viruses and combines to elicit immune responses against a variety of strains. The participants in the study were recruited from a dozen clinics across east Africa, South Africa, Thailand and the United States. This regimen is 1 of only 5 experimental HIV-1 vaccine concepts that has progressed to efficacy trials in humans in 35 years.
According to the authors, some of the study limitations include the lack of no definitive immunological measurement to predict protection against HIV-1 in humans and that “the relevance of vaccine protection in rhesus monkeys to clinical efficacy in humans” is not clear.
"These results should be interpreted cautiously. The challenges in the development of an HIV vaccine are unprecedented, and the ability to induce HIV-specific immune responses does not necessarily indicate that a vaccine will protect humans from HIV infection,” concluded Dr Barouch.
The phase 2b trial has been initiated in southern African evaluating the safety and efficacy of the vaccine candidate in 2,600 women at risk for HIV. The results of this trial will demonstrate if the vaccine has the potential to protect against the contraction of HIV.
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