A Phase 1/2a trial found that an experimental HIV-1 vaccine regimen was safe and induced immune responses against HIV in healthy adults and rhesus monkeys. The novel vaccine candidate was also shown to confer protection against infection with an HIV-like virus in monkeys. The full data were published in The Lancet

The APPROACH trial (N=393) aimed to test experimental regimens based on “mosaic” vaccines, which combine parts of different HIV viruses to generate immune responses against a range of HIV strains. The study’s authors assessed the mosaic adenovirus serotype 26 (Ad26)-based HIV-1 vaccine candidates in parallel studies to find the optimal regimen that would be evaluated in clinical efficacy trials. 

Healthy, uninfected adults aged 18 to 50 years were enrolled and randomized to 1 of 8 vaccine combinations or a placebo. Participants were primed at the start and at 12 weeks with an intramuscular injection of Ad26.Mos.HIV (5×1010 viral particles per 0.5mL) to induce an immune response and given boosters at weeks 24 and 48 with Ad26.Mos.HIV or modified vaccinia Ankara. 

The data showed all the evaluated vaccine regimens were able to generate anti-HIV immune responses in healthy individuals. The regimens were well-tolerated as evident by the comparable incidence of local and systemic reactions among all treatment arms. No grade 4 adverse events or death were reported. 

A parallel study evaluated the immunogenicity and efficacy of the same mosaic vaccine regimens in 72 rhesus  monkeys using a virus similar to HIV that affects monkeys. The data showed the Ad26/Ad26 plus gp140 vaccine generated the highest immune response in humans and conferred the best protection in monkeys. Specifically, the vaccine regimen provided 67% protection against viral challenge in monkeys, according to lead author Professor Dan Barouch, Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and Professor of Medicine at Harvard Medical School, Boston, MA. 

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Professor Barouch noted that the results should be viewed with caution, as the ability to induce HIV-specific immune responses “does not necessarily indicate that a vaccine will protect humans from HIV infection.”

A phase 2b clinical efficacy trial for this vaccine concept called Imbokodo (HVTN705) has been launched in southern Africa evaluating the candidate in 2,600 women at risk for acquiring the infection. 

For more information visit TheLancet.com.