Date Published: February 28, 2017
Publisher: Public Library of Science
Author(s): Linda-Gail Bekker, Glenda E. Gray
Abstract: In a Perspective, Linda-Gail Bekker and Glenda Gray discuss HIV vaccine development.
Partial Text: Importantly, a partially efficacious vaccine such as the one described in the recent modelling study has already been demonstrated. The RV144 vaccine trial was conducted amongst 16,395 heterosexual HIV-uninfected Thai adults using an ALVAC-HIV and AIDSVAX B/E gp120 boost regimen, and RV144 was the first vaccine to show any efficacy in reducing HIV acquisition, with a 60.5% (95% CI 22–80) efficacy within 12 months and a 31.2% (95% CI 1.1–52.1) efficacy after 3.5 years .
The breakthrough with RV144 was unexpected because, in the preclinical studies, ALVAC-HIV showed unimpressive immunogenicity and the protein boosts alone were unable to prevent HIV acquisition [9,10]. Additionally, there was a notable absence of stimulation of broadly neutralizing antibodies (BNAbs), the current popular target of new HIV vaccine research . BNAbs are a favoured topic in the HIV vaccine field because, once elicited, they are able to neutralize most strains of a viral pathogen, which would be highly desirable in the case of an HIV vaccine. BNAb responses do occur naturally in a small number of HIV-infected individuals, albeit years after infection. Key knowledge gaps have prevented a BNAb-focused vaccine approach, including the issues of how BNAbs develop and the mechanism by which the HIV virus drives their production. Isolated human samples from HIV-infected patients who do develop BNAbs have been studied, and this has provided some insight, from which immunogens have been designed . A proof-of-concept clinical trial to test whether one particular BNAb known as VRC01, which binds to the CD4 binding region of the HIV envelope, is effective in preventing HIV infection in women in the southern and eastern African region is currently underway. A companion trial evaluating this concept is being carried out in the Americas in MSM and transgender women. These trials will define whether HIV transmission at the mucosal level can be averted .
The findings of the HVTN 702 trial have the potential to be a great leap in HIV prevention research, with vaccine efficacy results anticipated in early 2021. But, even if efficacious, a paramount challenge will be getting the vaccine out of the laboratory and to those people who need it most—particularly, difficult-to-reach populations in low- and middle-income countries. Notably, the cost of vaccine manufacturing will play a large role, as developing countries are already having to make tough decisions regarding optimal funding of HIV prevention and treatment programs. If a vaccine is at best only partially efficacious, the correct combination of preventative measures will need to be explored, likely on a population-specific basis, and choices made. From current predictions, however, a safe vaccine of even modest efficacy could be the game changer necessary to close the HIV prevention gap.