April 5, 2012
Researchers Follow Up On Potential For HIV Vaccine
Researchers have discovered crucial hints into how immune system responses play a key role in protecting people from HIV infection. Results from the first ever RV144 HIV vaccine trial were published this week in the New England Journal of Medicine.
Scientists found that among Thai adults who received an experimental vaccine during a clinical trial, those who produced relatively high levels of a specific antibody after vaccination were less likely to become infected with the virus than those who did not.
Researchers from Walter Reed Army Institute of Research and Duke University collaborated with more than 25 institutions to analyze the data from the trial. After analyzing the data, researchers found that those receiving the vaccine regimen were 31.2 percent less likely to become infected with HIV.
“By studying those who became infected compared to those who did not, we believe we have found very important clues for how the RV144 trial might have worked,” said study coauthor Barton F. Haynes, M.D., Professor of Medicine and Immunology at Duke University. “The hypothesis is that protection in the trial was primarily mediated by antibodies.”
“All of the antibody types studied have been isolated from RV144 vaccines, and the antibodies' protective effect will be tested to see if they prevent acquisition of infection in non-human primate studies,” he added.
The analysis from the trial “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 (NIAID) Director Anthony S. Fauci, M.D. “With further exploration, this new knowledge may bring us a step closer to developing a broadly protective HIV vaccine.”
The results of the RV144 clinical trial, which involved more than 16,000 adult volunteers in Thailand, were first reported in 2009. Since then, more than a hundred scientists have been feverishly searching for molecular clues as to why the vaccine showed a modest protective effect.
The new report describes the researchers´ analyses of blood samples from a representative subset of the study participants: 41 who became infected after receiving the vaccine, and 205 who remained uninfected after receiving the vaccine. Those participants whose bodies produced relatively high levels of a particular antibody to HIV were much less likely to become infected than those who did not produce an antibody.
This particular binding antibody attaches to a part of the outer coat of the virus called the first and second variable regions (V1V2), which may play an important role in HIV infection of human cells. The antibody belongs to a family called immunoglobulin G, (IgG).
The researchers discovered that vaccinated study participants who had relatively high levels of a different type of HIV binding antibody, however, appeared to have less protection from the virus than vaccinated participants who had low levels of the protein.
This antibody attaches to a part of the virus´s outer coat called the first constant region (C1), and belongs to a family called immunoglobulin A (IgA). The study team hypothesizes that the C1 IgA antibody either was associated with less benefit from HIV vaccination or directly reduced the benefit of vaccination.
These findings, and the lab tests used in the studies, could help explain the effectiveness seen in RV144, and researchers plan to further evaluate the new findings in studies to be conducted in non-human primates using the RV144 vaccine regimen and other vaccines.
“The remarkable international collaboration to understand the RV144 study results has generated important hypotheses for scientists to investigate,” said Haynes.
More tests must also be conducted to determine whether high levels of V1V2 antibodies directly caused the modest protective effect 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.
Researchers noted that these results are unique to the RV144 regimen, and that different vaccines may protect against HIV in different ways. More research is needed to fully understand these results, and to determine if they can be generalized to other types of HIV vaccines or similar vaccines tested against other regional types of HIV.
The RV144 laboratory research was initiated and coordinated by the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research. The U.S. Army Medical Research and Materiel Command and the Bill and Melinda Gates Foundation co-funded the research along with NIAID.
Visit http://www.niaid.nih.gov/topics/hivaids/Pages/Default.aspx for more information about NIAID´s HIV vaccine research.