An experimental "mosaic" vaccine against a wide variety of HIV strains is well tolerated and produced comparable and robust immune responses in healthy adults and rhesus macaques, according to a new study published in The lancet,
Nearly 37 million people worldwide are living with HIV / AIDS, an estimated 1.8 million new cases each year. A safe and effective preventive vaccine is urgently needed to stem the HIV pandemic.
In the three decades of the HIV epidemic, only four vaccine concepts have been tested in humans, and only one has demonstrated protection in an efficacy study – a canarypox vector prime, gp120 boost vaccine that was tested in the RV144 study in Thailand Rate of human infection by 31%, but the effect was considered too low to bring the vaccine to general use.
A key hurdle for the development of HIV vaccines was 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 examined the leading mosaic adenovirus serotype 26 (Ad26) -based HIV-1 vaccine candidates in a randomized, double-blind, placebo-controlled trial Phase 1 / 2a trial (APPROACH).
Researchers included 393 healthy, HIV-1 uninfected participants (aged 18-50 years) who were at low risk for HIV-1 infection.
The volunteers were recruited from 12 clinics in East Africa, South Africa, Thailand and the US. They were randomized to either one of seven vaccine combinations or a placebo and received four vaccinations over a 48-week period.
To stimulate or "prepare" an initial immune response, each volunteer received an intramuscular injection of Ad26.Mos.HIV at baseline and again 12 weeks later.
The vaccine containing "mosaic" HIV Env / Gag / Pol antigens was produced by many HIV strains administered using a non-replicating common cold virus (Ad26).
To increase the level of the body's immune response, volunteers received two additional vaccinations at Weeks 24 and 48 using various combinations of Ad26.Mos.HIV or another vaccine component called Modified Vaccinia Ankara, with or without two different doses of Clade C HIV gp140 envelope protein containing an aluminum adjuvant.
The results showed that all tested vaccination regimens were able to produce anti-HIV immune responses in healthy subjects and were well tolerated, with a similar number of local and systemic responses reported in all groups, most of which were mild to moderate were.
Five participants reported at least one Level 3 adverse event related to the vaccine, including abdominal pain and diarrhea, posture and back pain. No adverse events or stage 4 deaths have been reported.
In a parallel study, the scientists investigated the immunogenicity and protective effect of the same Ad26-based mosaic vaccine in 72 rhesus monkeys with a series of repeated challenges using Simian-Human Immunodeficiency Virus – a virus similar to HIV that infects monkeys.
The Ad26 / Ad26 plus gp140 vaccine candidate induced the largest immune responses in humans and also provided the best protection in monkeys, resulting in complete protection against monkey immunodeficiency virus infection in two-thirds of the vaccinated animals after six challenges.
"Our results are an important milestone," said Professor Barouch.
"This study demonstrates that the Mosaic Ad26 prime, Ad26 plus gp140 boost HIV vaccine candidate induces robust immune responses in humans and monkeys with comparable size, kinetics, phenotype, and longevity, and also provided 67% protection against virus challenge in monkeys."
"These results should be interpreted with care," he added.
"The challenges of developing an HIV vaccine are unprecedented, and the ability to induce HIV-specific immune responses does not necessarily indicate that a vaccine protects people from HIV infection."
"We look forward to the results of the Phase 2b efficacy study HVTN705, which aims to determine if this vaccine protects humans from HIV infection."
Dan H. Barouch et al, Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomized, double-blind, placebo-controlled Phase 1 / 2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19). The lancet, published online on July 6, 2018; doi: 10.1016 / S0140-6736 (18) 31364-3