HIV Vaccine No Longer a Lofty Goal

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A viable vaccine remains the Holy Grail in efforts to prevent the spread of HIV and protect those at high risk for the virus.

A viable vaccine remains the Holy Grail in efforts to prevent the spread of HIV and protect those at high risk for the virus.

However, recent research suggests that a safe and effective vaccine for the virus that causes AIDS may be relatively close to becoming reality. A recent study published in the Annals of Internal Medicine assessed two vaccines for HIV-1—adenovirus serotype 26 with an HIV-1 envelope A insert (Ad26.EnvA) and adenovirus serotype 35 with an HIV-1 envelope A insert (Ad35.Env)—and concluded that both “elicited significant immune responses.” Furthermore, second administrations of both of these vaccines significantly boosted EnvA antibody titers. The study was funded by the International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute and Crucell Holland.

“We’re excited by these findings,” noted Lindsey R. Baden, MD, Associate Professor of Medicine, Harvard Medical School and one of the co-authors of the Annals study. “Developing a vaccine has been a challenge because HIV is a retrovirus that undermines the immune system; it also has latency and there isn’t any known adaptive immunity. But a vaccine can be really scalable globally, which is key to fighting this epidemic and which is why there is such a need.”

The international team of researchers for the Annals study, known as the B003-IPCAVD004-HVTN091 Study Group, performed a randomized, double-blind, placebo-controlled trial of the two vaccines, in which both participants and study personnel were blinded to treatment allocation. In all, 217 patients in the US, East Africa and South Africa received at least one vaccination with either Ad26.EnvA and/or Ad35.Env, both administered at a dose of 5 × 1010 viral particles. Those patients who received more than one administration received either the same vaccine they had been given initially or the other (homologous and heterologous regimens).

Of the enrolled patients, 210 (96.8 percent) completed follow-up, and there were no vaccine-associated serious adverse events reported. The authors found that both vaccines were generally well tolerated, and that they both elicited humoral and cellular immune responses in nearly all participants, even in patients with preexisting Ad26- or Ad35-neutralizing antibody titers.

Regardless of whether patients received one or both vaccine types, second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers), although the heterologous regimen of Ad26/Ad35 elicited significantly higher EnvA antibody titers than Ad35/Ad26. Interestingly, T-cell responses were modest and lower in East Africa than in South Africa and the United States. The authors also caution that because of the scope of the study the “durability of the immune responses” for both vaccines beyond one year remains unknown.

Dr. Baden and his colleagues are also quick to point out that studies such as theirs are merely a step in the process to developing a vaccine. Experts say there are trials of several vaccine approaches in process that should produce results over the next five years; however, that does not mean that there will be an effective, safe and affordable vaccine in that time. “We find [our] results very encouraging because these are the type of data to needed to figure out how to develop a vaccine and to design the proper field trials to determine if they work,” Dr. Baden told Contagion®. “Over the next five years, I think we’re likely to see some very important data emerge.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.

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