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Antibodies Protect Human Cells from Most HIV Strains

Atomic structure of the antibody VRC01 (blue and green) binding to HIV (grey and red). The site of VRC01-HIV binding is in red.NIAID Vaccine Research Center.

Scientists have isolated 2 potent human antibodies that can stop more than 90% of known global HIV strains from infecting human cells in the laboratory. The finding may help researchers design more effective HIV vaccines. It may also help advance other strategies for preventing or treating HIV infection.

Most vaccines work by triggering the immune system to produce antibodies that help beat back infections. This strategy hasn't been successful in defeating HIV. Proteins on the surface of HIV mutate rapidly and change shape continuously, preventing most antibodies from latching onto and neutralizing the virus.

Researchers have recently found antibodies that can neutralize multiple strains of HIV-1, the virus responsible for the HIV/AIDS pandemic. These antibodies bind to a specific, virtually unchanging region on HIV’s surface spikes—the structures that help the virus attach to and infect immune cells. Much attention has focused on a surface spike protein called gp120, which fastens onto the CD4 binding site on the surface of immune cells.

A team of scientists led by Drs. John R. Mascola and Gary J. Nabel of NIH's National Institute of Allergy and Infectious Diseases (NIAID) set out to isolate even more broadly neutralizing antibodies. Guided by recent insights into how HIV binds CD4, they used computer-assisted design to make protein probes that would react only with antibodies specific to the unchanging area where the virus binds CD4. The researchers then used the probes to isolate antibody-producing B cells from the serum of an HIV-1-infected donor.

In the advance online edition of Science on July 8, 2010, the scientists reported finding 3 antibodies, called VRC01, VRC02 and VRC03. The first 2 of these antibodies are able to neutralize over 90% of circulating HIV-1 isolates. The antibodies are also more potent than previously identified HIV-neutralizing antibodies.

"The antibodies attach to a virtually unchanging part of the virus, and this explains why they can neutralize such an extraordinary range of HIV strains," Mascola explains.

In a companion paper, a collaborating group led by NIAID's Dr. Peter D. Kwong explored the atomic-level structure of VRC01 when attached to the CD4 binding site. Their analysis offered insights into how researchers might elicit VRC01-like antibodies through vaccination. "The discoveries we have made may overcome the limitations that have long stymied antibody-based HIV vaccine design," Kwong says.

“The discovery of these exceptionally broadly neutralizing antibodies to HIV and the structural analysis that explains how they work are exciting advances that will accelerate our efforts to find a preventive HIV vaccine for global use,” says NIAID director Dr. Anthony S. Fauci. “In addition, the technique the teams used to find the new antibodies represents a novel strategy that could be applied to vaccine design for many other infectious diseases.”