IAVI investigators awarded grant to examine antibodies that neutralize HIV virus

A team of investigators headed by International AIDS Vaccine Initiative (IAVI) Investigator Pascal Poignard has been awarded a major grant from the National Institute of Allergy and Infectious Diseases (NIAID) of the US National Institutes of Health (NIH) to investigate the biological mechanisms underlying the generation of broadly neutralizing antibodies by HIV positive individuals. The research is designed to explore why they develop in a minority of individuals and what factors contribute to their emergence following infection by HIV. These antibodies, which can bind to and disable a wide spectrum of HIV variants, are thought to hold valuable clues to the effective design of AIDS vaccines; if a vaccine could elicit such antibodies, it is believed, it would be highly effective. Researchers at and affiliated with IAVI and at the NIH's Vaccine Research Center have recently discovered several particularly potent and broadly neutralizing antibodies against HIV.

The U19 grant, which the NIH issues to support research programs involving the participation of multiple scientific collaborators, will provide US $7.8 million to fund the coordinated investigations of four leading academic laboratories and the contributions of three support groups. The researchers will have access to blood samples and relevant data from cohorts of HIV positive volunteers in the US and five sub-Saharan African countries. IAVI's Poignard is a physician and immunologist whose laboratory is located at the IAVI Neutralizing Antibody Center at The Scripps Research Institute in La Jolla, California, which was opened in 2009. "This program will provide valuable information to researchers around the world who are engaged in efforts to develop vaccines against HIV," said Wayne Koff, Senior Vice President of Research and Development at IAVI. "We expect that it will help address what is perhaps the most significant impediment to the development of effective AIDS vaccines: the generation of antibodies that are versatile enough to disable the majority of the variants of HIV."

Recent studies suggest that between 10 and 20 percent of HIV positive individuals generate broadly neutralizing responses, typically doing so only three to four years after HIV infection. What is unknown is why and how those individuals develop such responses. "We expect that the biological explanations for the development of broadly neutralizing antibody responses," says Poignard, "are likely to be of special relevance to the design of candidate AIDS vaccines and immunization regimens devised to elicit similar antibodies."

In pursuit of those explanations, Poignard and his colleagues will investigate what differentiates the HIV infections and immune responses of those who produce broadly neutralizing antibodies from those who do not. Their studies will use samples that have been collected from two cohorts of HIV positive volunteers whose health has been systematically tracked from the very beginning of their infections. One group comes from a study called Protocol C, which was established in Africa with IAVI's sponsorship to enable precisely these kinds of investigations and has already enrolled about 500 individuals recently infected with one of three different major subtypes of HIV-1 (clades A, C and D). The second group, the First Choice Cohort of more than 100 individuals in San Diego, is a project funded by NIAID.

The researchers involved in the U19 program are led by the following investigators:

• Pascal Poignard, the Program Director, a Principal Investigator at the IAVI Neutralizing Antibody Center and an Adjunct Professor in the Department of Immunology and Microbial Science at the Scripps Research Institute.
• J. Christopher Love, an Assistant Professor in Chemical Engineering at the Massachusetts Institute of Technology, Associate Member at the Eli and Edythe L. Broad Institute and Associate Faculty at the Ragon Institute. Shane Crotty, an Associate Professor with tenure at the La Jolla Institute for Allergy and Immunology and an adjunct professor at the University of California, San Diego.
• Davey M. Smith, a physician and an Associate Professor in the Department of Medicine and Division of Infectious Diseases at the University of California, San Diego, where he also directs the Centers for AIDS Research Translational Virology Core.
• A Protein Production Core will be led by Simon Hoffenberg, a Principal Scientist at the International AIDS Vaccine Initiative and an Assistant Professor at SUNY Downstate Medical Center.
• A Data Management Core will be led by Sergei L. Kosakovsky Pond, an Assistant Professor in the University of California, San Diego Department of Medicine (Divisions of Biomedical Informatics and Infectious Diseases).
• Finally, Poignard will also lead an Administrative Core that will coordinate the entire effort, providing scientific leadership and fiscal and personnel management for the overall program.

IAVI is confident that this closely coordinated and multidisciplinary program of research into HIV neutralization will contribute significantly to its mission to ensure the development of safe and effective AIDS vaccines for use throughout the world. More than 25 million people have died of HIV-related causes since the start of the pandemic, and every day 7,400 people are newly infected by the virus. Unraveling the broadly neutralizing antibody problem is, for this reason, one of the most pressing challenges facing modern medical science: its solution may well hold the key to an AIDS vaccine. IAVI applauds the NIH for its support for this vitally important program of research.