IAVI Establishes HIV Neutralizing Antibody Consortium

By Emily Bass

IAVI, the National Institutes of Health Vaccine Research Center (VRC) and a number of leading laboratories have formed an HIV Neutralizing Antibody Consortium (NAC) that will intensify work on one of the AIDS vaccine field’s most enduring challenges:

making antibodies that neutralize a broad range of HIV strains. The consortium will target funding to projects that make more direct links between basic science research on neutralizing antibodies (Nabs) and vaccine product development, and will facilitate closer collaboration among some of the field’s foremost antibody researchers and their institutions, including: Dennis Burton (Consortium Director, Scripps Research Institute), Ian Wilson (Scripps Research Institute), Robert Doms (University of Pennsylvania), John Moore (Cornell University Medical College) and Joe Sodroski (Harvard Medical School), as well as Gary Nabel, Richard Wright and Peter Kwong of the VRC.

 

Neutralizing antibodies are Y-shaped immune proteins that bind free HIV and prevent it from infecting cells. They are thought to be an important component of the protection generated by many licensed viral vaccines, including polio and hepatitis B. In the AIDS field, experiments with macaques have found that passive transfer of HIV-specific antibodies can protect against challenge with SIV/HIV hybrid viruses. Since NAbs attack virus before it has entered cells, they could conceivably stop HIV—which must enter cells to replicate—from infecting the body. It’s widely believed that these immune responses will be crucial to vaccines that prevent the establishment of HIV infection.

The NAC will intensify efforts to induce these responses and to identify NAb-inducing immunogens that can be used either independently or together with the current generation of AIDS vaccines, which stimulate HIV-specific cell-mediated immune responses (including CD4 and CD8 T-cells). These responses target cells that are already infected with HIV, and in macaques can prevent or delay disease but cannot completely block infection. For this reason, many researchers are convinced that the most effective AIDS vaccines will need to induce both cellular and antibody-based (humoral) immunity.

So far, the AIDS vaccine field has yet to realize the goal of inducing broad NAbs. One obstacle is the rapid rate of mutation in the HIV envelope, which contains key NAb binding sites, allowing the virus to evolve away from potential NAbs. The envelope’s three-dimensional structure also thwarts NAb binding through a complex folding that tucks key regions deep inside the protein, underneath a thick outer coating of sugar molecules.

“With the NAC, IAVI has committed to a five-year, multimillion dollar effort,” says Wayne Koff, IAVI’s Vice President for Research and Development. “The NAC will help ensure that an all-out effort is made to solve the problem of designing immunogens that can stimulate NAbs against HIV.” Funds will be used for research in two broad categories: structural biology and immunogen design. Projects will focus on elucidating the detailed 3-D structure of the envelope protein and understanding the structure of complexes formed when HIV binds to the surface of CD4 target cells. Based on knowledge gained from these studies, the NAC will then design immunogens aimed at generating NAbs in a vaccine strategy. “The unique aspect of the NAC is its linkage of leading labs working on this problem in a way that allows flexible use of resources,” says Koff. “We will try whatever it takes to solve this problem.”

NAC intellectual property agreements will provide IAVI with the option of a license to develop any potential products from the consortium, to fulfill IAVI’s mission of ensuring that developing countries can access successfully licensed vaccines at reasonable cost.