Investigational HIV Vaccine Effective, Well-Tolerated Among Patients

Findings from an early-stage clinical trial suggest that an investigational HIV vaccine is well-tolerated and can elicit an effective immune response against the virus in healthy adults.

Results from the APPROACH trial will determine whether clinical testing will advance to a large study in South Africa to explore the safety and efficacy of the vaccine among women at high-risk of HIV, according to the National Institutes of Health (NIH).

The investigational HIV vaccine regimens are based on mosaic vaccines, which are designed to elicit immune responses against a variety of HIV subtypes found around the world. Different subtypes of the virus dominate certain parts of the world.

In preclinical trials, these regimens were observed to protect monkeys against an HIV-like virus. The most effective regimen reduced the risk of infection by 94% and protected 66% of monkeys against the virus after 6 exposures, according to a press release.

“A safe and effective HIV vaccine would be a powerful tool to reduce new HIV infections worldwide and help bring about a durable end to the HIV/AIDS pandemic,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Disease. “By exploring multiple promising avenues of vaccine development research, we expand our opportunities to achieve these goals.”

Included in the clinical trial were nearly 400 patients from the United States, Rwanda, Uganda, South Africa, and Thailand. Patients were randomized to receive 1 of 7 investigational vaccines or placebo. Patients received 4 vaccines over 48 weeks, which included 2 doses of the prime vaccine, followed by 2 doses of a booster vaccine, according to the NIH.

All of the regimens included the same components in the prime vaccine, known as Ad26.Mos.HIV. The prime vaccines used a strain of the adenovirus serotype 26 (Ad26) as a vector to deliver the antigens, while the booster vaccine included combinations of the Ad26.Mos.HIV components, MVA-Mosaic, and/or 2 different doses of subtype C HIV gp140 envelope protein containing an aluminum adjuvant to up immune response, according to the release.

After the third vaccination, patients were observed to develop an antibody and immune response against HIV. The booster vaccines were observed to change the immune response in patients. Interestingly, the vaccine that was most protective in preclinical animal studies was found to bolster the strongest immune response in human patients, which is not always the case.

The anti-HIV immune response was observed to be heightened after the fourth vaccination, according to the release.

The authors concluded that additional studies would explore the regimen that includes 2 Ad26 mosaic primes and 2 boosters with Ad26 mosaic and subtype C gp140, according to the release.

The researchers reported that the different mosaic vaccines were well-tolerated and created an anti-HIV immune response in HIV-negative patients, the NIH reported.

Despite the promising results, additional research is needed because the ability to elicit immune responses may not indicate that a vaccine can prevent HIV infection, according to the authors.

The results from the APPROACH clinical trial support further validation of the regimens in a clinical trial to explore their safety and efficacy in South Africa. The authors expect to enroll up to 2600 HIV-negative women.

“The promising, early-stage results from the APPROACH study support further evaluation of these candidate vaccines to assess their ability to protect those at risk of acquiring HIV,” said principal investigator Dan H. Barouch, MD, PhD.