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New Studies Enhance Knowledge of Antibodies in HIV Vaccine Trials

March 19, 2014
New findings highlight the role antibodies appear to play in decreasing the risk of HIV infection during the RV144

Two studies in the March 19 issue of Science Translational Medicine shed new light on the antibodies that appear to have played a role in decreasing the risk of HIV infection in the RV144 HIV vaccine trial. The results provide a better understanding of the immune response a vaccine may need to elicit in order to provide protection from HIV.

In a previous analysis of RV144 results, researchers found that a type of antibody called IgG that binds to a specific part of the HIV virus—the V1V2 region of HIV’s Envelope protein or “outer coat”—correlated with lower infection rates among those who were vaccinated. 

The new findings, which compared the VAX003 and RV144 HIV vaccine trials, suggests that it was a specific subclass of IgG antibody, IgG3, that was associated with the decreased risk of infection and that this particular antibody might be responsible for directing a coordinated attack on HIV.

In a study led by the Duke Human Vaccine Institute (DHVI), researchers found that IgG3 antibodies were more likely to be found in those who received the vaccine regimen in the RV144 trial (a prime boost combination of two vaccines: ALVAC® and AIDSVAX® B/E) compared to those in the VAX003 trial (AIDSVAX® B/E alone). In the RV144 trial, 31.2% of those vaccinated were protected from HIV. The VAX003 regimen showed no efficacy, yet it generated higher levels of other types of antibodies in recipients. 

Additionally, Duke researchers found that the amount of IgG3 antibodies in the vaccine recipients’ blood diminished over time similar to the waning efficacy observed in the RV144 trial. More research is needed to determine if there is a relationship between the decline in antibodies and vaccine efficacy.

In a separate study that compared the antibody functionality between the two trials, researchers at the Ragon Institute of MGH, MIT, and Harvard showed that the RV144 vaccine regimen induced several antibodies that were able to lead a coordinated attack on HIV and that it was IgG3 antibodies that largely conducted these “HIV-eliminating” activities. Researchers also noted that the higher efficacy seen in RV144 may be due to higher levels of IgG3 generated against a particulary vulnerable region of HIV’s outer coat called the V2-loop.

“Taken together, these results suggest that IgG3 might be the key difference between the efficacy outcomes of the VAX003 and RV144 HIV vaccine trials,” said Col. Jerome Kim, deputy director of the U.S. Military HIV Research Program (MHRP) and study author. “We now know more about the attributes of the antibodies that may play a role in reducing the risk of HIV infection.” 

“The field continues to work together to dissect the mechanisms of risk of infection observed in the RV144 study,” said MHRP Director Col. Nelson Michael. “This is both defining new pathways for us to explore moving forward in HIV vaccine development and growing synergies within the field to ensure that we are moving as swiftly as possible.”