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New Study Provides Additional Insights into V2 Antibodies in the RV144 Trial
A new study, led by a team at Duke Medicine and including researchers from the NIH Vaccine Research Center, MHRP, and the Thailand Ministry of Public Health, has provided additional insights into the workings of the RV144 vaccine. The findings, reported in the journal Immunity, are providing new options for vaccine designers to strengthen the vaccine.
“This study shows what types of antibodies the vaccine induced and gives us information that can guide the study of future vaccine trials,” said senior author Barton Haynes, M.D., director of the Duke Human Vaccine Institute. “Understanding how this vaccine works is important to develop strategies to make it better.”
Since the results of RV144 were announced in 2009, researchers have been studying the vaccine for clues to its successes and failures in the hopes of making improvements. Two major studies were published in the last year that focus on the immune responses directed at a particular region—the V2 region— of the HIV virus envelope, which researchers associated with reduced infection.
“We continue to build on the RV144 results, and gain insights into how the immune system can effectively fight HIV,” Said Col. Jerome Kim, Principal Deputy at MHRP. "These studies shed light on the types of antibodies, generated by the vaccine, that may be associated with a decreased risk of infection.” Although none of the antibodies studied was in the class called 'broadly neutralizing', Dr. Haynes and his colleagues found that some of the antibodies from RV144 volunteers appeared to bind the virus at some of the same places that broadly neutralizing antibodies do.
In the current study, the researchers have strengthened the association between the vaccine-induced antibodies and found important characteristics of the antibodies induced by the vaccine. Analyzing the immune responses produced by three vaccine recipients in the original trial, the researchers isolated four key antibodies that targeted the V2 region.
In spite of variations in the V2 site’s structure, the antibodies zeroed in on the virus, specifically binding at a position on the outer coating of the virus that was already known for attracting immune warriors known as neutralizing antibodies.
Researchers found that the four vaccine-triggered antibodies worked differently than the neutralizing antibodies. Instead of attacking the virus directly, the vaccine-induced antibodies recognized virus-infected cells and flagged them for an attack by other immune cells.
The findings suggest that these types of V2 antibodies expand the immune system’s arsenal against HIV, so if they can improve these V2 responses, that might provide a way to improve the level of protection seen in original RV144 study.
“The next step for our research is to explore how to design immunogens to induce antibodies that can have broader responses to attack more virus types,” said Hua-Xin Liao, MD, PhD, lead author and research director of Duke Human Vaccine Institute. In addition to Haynes and Liao, study authors include MHRP Principal Deputy, Col. Jerome H. Kim; MHRP Director, Col. Nelson L. Michael; and MHRP scientists Mangala Rao and Kristina K. Peachman.