April 9, 2012
HIV Vaccine Study Offers Up Possible Antibody Protection Clues
by Reed Vreeland
Scientists continued to unravel clues as to why a combination of two preventive HIV vaccines—ALVAC HIV and AIDSVAX B/E—may have worked for some but not others in a large scale clinical trial reported in 2009. A new paper published online ahead of print in The New England Journal of Medicine (NEJM) suggests those who produced relatively high levels of a specific antibody after receiving the vaccinations in study RV 144 were less likely to become infected with HIV, compared with those who did not.
“This analysis has produced some intriguing hints about what types of human immune responses a preventive HIV vaccine may need to induce,” said National Institute of Allergy and Infectious Diseases director Anthony S. Fauci, MD, in a news announcement highlighting the post-study data analysis. “With further exploration, this new knowledge may bring us a step closer to developing a broadly protective HIV vaccine.”
In the RV 144 clinical trial, which involved more than 16,000 adult volunteers in Thailand, the group that received ALVAC HIV and AIDSVAX B/E had a 31 percent lower chance of becoming infected with HIV than the group that received a placebo. Initially, the difference between the two groups was considered to be statistically significant—modest, but great enough to have not occurred by chance. A second statistical analysis, however, failed to confirm a statistically significant difference between the two groups.
Still, a consortium of scientists has remained dedicated to searching for molecular clues to explain why the vaccines at least showed a trend toward benefit.
The new report describes an analysis of blood samples taken from a subset of study participants, notably 41 who were vaccinated and later became infected with HIV and 205 vaccinated participants who remained uninfected.
The participants who made relatively high levels of one antibody to HIV were significantly less likely to become infected than those who did not. This particular binding antibody attaches to a part of the outer coat of the virus called the first and second variable regions, or V1V2, which may play an important role in HIV infection of human cells. The antibody belongs to a family called immunoglobulin G, or IgG.
Conversely, high levels of a different type of HIV binding antibody—an immunoglobulin A, or IgA, antibody that attaches to another part of the virus’s coat, known as the first constant region, or C1—was associated with less protection against infection with the virus. According to the scientists, under the direction of Barton Haynes, MD, of Duke Human Vaccine Institute in Durham, North Carolina, the C1 IgA antibody either was associated with less benefit from HIV vaccination or directly reduced the benefit of vaccination.
Next up, scientists will conduct primate studies to determine whether high levels of V1V2 antibodies directly caused the modest protective effect seen in the RV 144 study or simply were linked to other, still unidentified factors responsible for the trial’s encouraging outcome. Such testing also will determine whether the V1V2 antibody response is merely a marker of HIV exposure or decreased susceptibility to HIV infection.
The study authors note that different vaccine candidates may protect against HIV in different ways. Therefore, more research is needed to understand whether these new findings will be relevant to other types of HIV vaccines or to similar vaccines tested against HIV strains from other regions or against different routes of exposure to the virus.
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