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The Bill & Melinda Gates Foundation has awarded three grants to the Duke University Medical Center for HIV projects in the Collaboration for AIDS Vaccine Discovery (CAVD) program. The total amount of all three grants is about $37.2 million.

A five-year, $24.6 million grant from the Gates Foundation will allow David Montefiori, PhD, professor of surgery and director of the Laboratory for AIDS Vaccine Research and Development in the Department of Surgery and his collaborators to continue their efforts. Their first CAVD grant began with a five-year, $31.5 million award from the Gates Foundation in 2006.

The original grant allowed them to establish the Comprehensive Antibody Vaccine Immune Monitoring Consortium (CAVIMC). The new grant will allow the consortium to operate on a lower budget, because several discovery projects were completed during the first five years.

"The goal of the CAVIMC is to facilitate the discovery and timely licensure of a safe, effective and practical HIV vaccine for the world," Montefiori said. "We aim to accomplish this by using valid laboratory criteria and good clinical laboratory practices (GCLP) to monitor antibody responses in the systemic and mucosal compartments in preclinical and clinical phases of vaccine testing. We also aim to identify correlates of protective immunity and to generate new scientific findings that will help bridge the gap between preclinical vaccine discovery and human clinical trials."

Montefiori noted that the outcome of the recent Thai trial called RV144 has generated optimism that a broadly effective HIV vaccine is finally within reach. The CAVIMC consortium will take the lessons learned from this trial and translate them into a stronger laboratory program for HIV vaccine discovery and licensure.

Barton Haynes, MD, a national leader in AIDS/HIV research and director of the Center for HIV/AIDS Vaccine Immunology (CHAVI), as well as director of the Duke Human Vaccine Institute (DHVI), has won a new award to study the best way to create effective immunogens that mimic the proteins on the HIV outer envelope that will help to stimulate the right antibodies to neutralize the virus at the time of transmission. The grant will provide $11.7 million over three years.

The research team will focus on evaluating antibodies as candidates for correlates of protection that we are learning about from the RV144 trial in Thailand, said Haynes, who is Frederic M. Hanes Professor of Medicine and Immunology.

Haynes led a multinational, in-depth correlates-of-protection analysis of the RV144 Thai efficacy trial results, which showed that a combination of vaccines lowered the rate of HIV infection 31 percent compared to placebo in the population, but that the protective effect was short-lived. The immune correlates analysis identified two types of antibodies that correlated with infection risk.

Haynes' new grant will study the mechanisms of effects of these two RV144-induced antibody types. In this research, he will work closely with the Montefiori team.

Michael Frank, MD, a professor of pediatrics and immunology, is new to the CAVD and won a grant for more than $892,000 over three years.

His work involves the study of complement proteins, which play a role in host defense and are part of the innate immune system; that is, these proteins are present even before a person receives a vaccine and is immunized. The complement proteins coat viral envelope antigens with peptides that facilitate ingestion by cells called phagocytes that act to destroy a microbe, Frank said. Complement coating of antigens also facilitates the immune response.

"We made the observation that intact HIV envelope antigen binds complement poorly or not at all, and postulate that this contributes to the poor response to viral antigen," said Frank. "We believe that failure to bind complement contributes to the poor antibody response in HIV vaccine recipients immunized to prevent HIV infection. We also find that the intact HIV envelope antigen has a very short half-life in vivo that further contributes to the poor response to the vaccine."

The group plans to modify the HIV antigen so that it is able to bind the appropriate complement proteins, and they also intend to stabilize the protein so that it is not broken down rapidly and thus can contribute to a normal, effective immune response.