Research results from 2 studies found that the mosaic Ad26–based HIV vaccine regimens were both well-tolerated and induced a robust immune response against HIV in healthy adults and rhesus monkeys.
As researchers worldwide work toward creating a vaccine for HIV, new study results indicate that an experimental mosaic HIV vaccine may have the potential to protect against a wide range of global HIV strains.
Researchers conducted 2 studies and observed that mosaic Ad26—based HIV vaccine regimens were both well-tolerated and induced a robust immune response against HIV in healthy adults and rhesus monkeys.
In the APPROACH trial of nearly 400 participants, researchers conducted a multicenter, randomized, double-blind, placebo-controlled study to assess the safety, tolerability, and immunogenicity of several vaccine regimens in humans. They recruited 393 HIV-uninfected adults age 18 to 50 from the United States, east Africa, South Africa, and Thailand between February 2015 and October 2015. Participants either received 4 vaccinations over 48 weeks—2 doses of a prime vaccine followed by 2 doses of a booster vaccine—or placebo.
For the prime vaccine, used to stimulate an initial immune response, participants were injected with Ad26.Mos.HIV, which uses a strain of the common-cold virus. The 2 boost vaccinations used various combinations of Adv.Mos.HIV or Modified Vaccina Ankara, with or without 2 different doses of clade C HIV gp 140 envelope protein containing an aluminum adjuvant.
Results of the vaccine showed all regimens were capable of generating anti-HIV immune responses and were well tolerated in the healthy participants.
“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 Dan H. Barouch, MD, PhD, director, the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, professor of medicine at Harvard Medical School, and principal investigator of the study, in a statement.
In a parallel study—NHP 13-19—the researchers examined the immunogenicity and protective efficacy of the same vaccine regimens in 72 rhesus monkeys. The Ad26/Ad26 plus gp 140 regimen, which stimulated the highest immune response in humans, also yielded the best protection in monkeys, resulting in complete protection against simian-human immunodeficiency virus—a virus similar to HIV that infects monkeys—in two-thirds of the monkeys.
Encouraged by the results, the researchers wrote: “Previous HIV-1 vaccine candidates have typically been limited to specific regions of the world. Optimized mosaic antigens offer the theoretical possibility of developing a global HIV-1 vaccine.”
The results of the studies have now lead to the initiation of a phase 2b trial in southern Africa to determine the safety and efficacy of the vaccine in 2600 women at risk for contracting HIV.
Barouch D, Tomaka F, Wegmann F, et al. Evaluation of mosaic HIV-1 vaccine in a multicenter, randomized, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19) [published online July 6, 2018]. Lancet. doi: http://dx.doi.org/10.1016/ S0140-6736(18)31364-3.