An experimental ‘mosaic’ vaccine against a wide variety of HIV strains is well-tolerated and generated comparable and robust immune responses in healthy adults and rhesus macaques, according to a new study published in The Lancet.

Almost 37 million people worldwide are living with HIV/AIDS, with an estimated 1.8 million new cases every year. A safe and effective preventative vaccine is urgently needed to curb the HIV pandemic.

In the three decades of the HIV epidemic, only four vaccine concepts have been tested in humans, and only one has provided evidence of protection in an efficacy trial — a canarypox vector prime, gp120 boost vaccine regimen tested in the RV144 trial in Thailand lowered the rate of human infection by 31% but the effect was considered too low to advance the vaccine to common use.

A key hurdle to HIV vaccine development has been the lack of direct comparability between clinical trials and preclinical studies.

To address these issues, Professor Dan Barouch of Beth Israel Deaconess Medical Center and Harvard Medical School and co-authors evaluated the leading mosaic adenovirus serotype 26 (Ad26)-based HIV-1 vaccine candidates in a randomized, double-blind, placebo-controlled phase 1/2a trial (APPROACH).

The researchers included 393 healthy, HIV-1-uninfected participants (aged 18-50 years) who were considered at low risk for HIV-1 infection.

The volunteers were recruited from 12 clinics in east Africa, South Africa, Thailand, and the United States. They were randomly assigned to receive either one of seven vaccine combinations or a placebo, and were given four vaccinations over the course of 48 weeks.

To stimulate, or ‘prime,’ an initial immune response, each volunteer received an intramuscular injection of Ad26.Mos.HIV at the start of the study and again 12 weeks later.

The vaccine containing ‘mosaic’ HIV Env/Gag/Pol antigens was created from many HIV strains, delivered using a nonreplicating common-cold virus (Ad26).

To ‘boost’ the level of the body’s immune response, volunteers were given two additional vaccinations at week 24 and 48 using various combinations of Ad26.Mos.HIV or a different vaccine component called Modified Vaccinia Ankara with or without two different doses of clade C HIV gp140 envelope protein containing an aluminium adjuvant.

The results showed that all vaccine regimens tested were capable of generating anti-HIV immune responses in healthy individuals and were well tolerated, with similar numbers of local and systemic reactions reported in all groups, most of which were mild-to-moderate in severity.

Five participants reported at least one vaccine-related grade 3 adverse event such as abdominal pain and diarrhea, postural dizziness, and back pain. No grade 4 adverse events or deaths were reported.

In a parallel study, the scientists assessed the immunogenicity and protective efficacy of the same Ad26-based mosaic vaccine regimens in 72 rhesus monkeys using a series repeated challenges with simian-human immunodeficiency virus — a virus similar to HIV that infects monkeys.

The Ad26/Ad26 plus gp140 vaccine candidate induced the greatest immune responses in humans and also provided the best protection in monkeys, resulting in complete protection against simian-human immunodeficiency virus infection in two-thirds of the vaccinated animals after six challenges.

“Our results represent an important milestone,” Professor Barouch said.

“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.”

“These results should be interpreted cautiously,” he added.

“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.”

“We eagerly await the results of the phase 2b efficacy trial called HVTN705, which will determine whether or not this vaccine will protect humans against acquiring HIV.”

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Dan H. Barouch et al. Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19). The Lancet, published online July 6, 2018; doi: 10.1016/S0140-6736(18)31364-3