Researchers Discover Broadly Neutralizing Antibodies that Act Against 91% of HIV Strains

Researchers with the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center have identified 2 new antibodies, dubbed VRC01 and VRC02, that can neutralize more than 90% of know HIV strains, according to reports in the July 8, 2010 advance online edition of Science. These antibodies -- which target a conserved (mutation-resistant) part of the HIV gp120 envelope protein that attaches to the CD4 surface receptor to enter cells -- could potentially be used to create a future preventive vaccine, protective microbicide, or therapeutic vaccine to slow disease progression in people already infected.

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Additional ALVAC/AIDSVAX HIV Vaccine Data Show Only Modest Benefit with Minimal Statistical Significance

A closer look at complete data from an HIV vaccine trial in Thailand indicates that the results are less impressive than suggested when partial results were announced last month. The ALVAC/AIDSVAX vaccine combination showed a moderate protective effect according to one type of analysis, investigators said at the AIDS Vaccine 2009 conference this week in Paris, but the full analysis indicates that the results could have been due to chance.

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Scientists at the U.S. National Institutes of Health Discover Human Antibodies That Can Stop Most HIV Strains from Infecting Human Cells

Researchers have found 2 human antibodies that, in laboratory testing, halt the infection of more than 90 known strains of HIV, according to scientists at the National Institutes of Health (NIH). This discovery could lead to more effective HIV vaccines and to improved strategies for the prevention and treatment of HIV infection.

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Phase 3 Study in Thailand Shows First Evidence that HIV Vaccine Can Reduce Rate of Infection

In a Phase 3 clinical trial with more than 16,000 participants, volunteers who received a prime-boost combination of the ALVAC HIV and AIDSVAX B/E vaccines were 31% less likely to become infected with the virus than those who received placebo injections, according to an announcement from the U.S. Military HIV Research Program.

The trial -- known as RV144 -- was a proof-of-concept study designed to evaluate the ability of the vaccine combination both to prevent infection and to maintain a lower viral load in people who did become infected.

The study, which took place in Thailand starting in 2003, was conducted by a collaboration including the U.S. Military HIV Research Program (MHRP), the Thai Ministry of Public Health, the National Institute of Allergy and Infectious Diseases (part of the National Institutes of Health), Sanofi Pasteur, and Global Solutions for Infectious Diseases (GSID).

A total of 16,402 initially HIV negative men and women aged 18-30 years were randomly assigned on a 1-to-1 basis to receive either the vaccine combination or placebo injections. The vaccine group first received a priming vaccine, known as ALVAC HIV (developed by Sanofi-Pasteur), followed by a booster shot, known as AIDSVAX B/E (originally developed by VaxGen, now licensed to GSID). Both genetically engineered vaccines carry genes from HIV strains prevalent in Southeast Asia.

Vaccine or placebo injections were administered within a 6-month period. Participants were then followed for an additional 3 years, receiving HIV prevention counseling and HIV tests every 6 months.

In the final analysis, 51 vaccine recipients became infected with HIV compared with 74 placebo recipients, a statistically significant difference. While the vaccine combination was characterized as "modestly effective" -- decreasing the rate of infection by 31.2% -- even a small reduction could make a considerable difference on a population-wide basis in areas where HIV prevalence is high.

"This is the first HIV vaccine candidate to successfully reduce the risk of HIV infection in humans," said U.S. Army Surgeon General Lt. General Eric Schoomaker in a MHRP press release. "We are very excited and pleased with the outcome of this trial and congratulate all those who participated in it."

These results are a welcome surprise, since HIV vaccine research to date has proven disappointing. In 2003, investigators reported that AIDSVAX (based on the HIV gp120 envelope protein) did not prevent infection when used alone. In another previous trial, HIV positive participants who received ALVAC HIV (HIV genes carried by a disabled canarypox vector) as a therapeutic vaccine not only failed to achieve a lower viral load, but had to resume antiretroviral therapy sooner due to disease progression. Most recently, in the STEP trial, Merck's V520 vaccine (HIV genes with an adenovirus vector) neither prevented infection nor lowered viral load among those infected.

But the results of the RV144 trial may rekindle some optimism in the field.

"These results show that development of a safe and effective preventive HIV vaccine is possible," said MHRP Director Colonel Nelson Michael. "While these results are very encouraging, we recognize that further study is required to build upon these findings."

"The outcome is very exciting news and a significant scientific achievement," International AIDS Vaccine Initiative (IAVI) president Seth Berkley said in a statement posted on the organization's web site, "It's the first demonstration that a candidate AIDS vaccine provides benefit in humans. Until now, we've had evidence of feasibility for an AIDS vaccine in animal models. Now, we've got a vaccine candidate that appears to show a protective effect in humans, albeit partially."

Detailed results from the study will be presented at the AIDS Vaccine Conference, to be held October 19-22 in Paris.

9/25/09

Source

U.S. Military HIV Research Program. HIV Vaccine Study First to Show Some Effectiveness in Preventing HIV. Press release. September 24, 2009.

International AIDS Vaccine Initiative. IAVI Statement on Results of Phase III ALVAC-AIDSVAX Trial in Thailand. Press release. September 24, 2009.