Scientists have discovered two potent human antibodies that can stop more than 90 percent of known global HIV strains from infecting human cells in the laboratory. The scientists also have demonstrated how one of these disease-fighting proteins accomplishes this feat. According to the scientists, these antibodies could be used to design improved HIV vaccines, or could be further developed to prevent or treat HIV infection. Plus, the method used to find these antibodies could be applied to isolate therapeutic antibodies for other infectious diseases as well.
Led by a team from the NIAID Vaccine Research Center (VRC), the scientists found two powerful antibodies called VRC01 and VRC02 in an HIV-infected individual's blood. They discovered the antibodies using a probe they developed that homes in on the specific cells that make antibodies against a very vulnerable spot on HIV.
The scientists found that VRC01 and VRC02 neutralize more HIV strains with greater overall strength than previously known antibodies to the virus.
Atomic structure of the antibody VRC01 (blue and green) binding to HIV (grey and red). The precise site of VRC01-HIV binding (red) is a subset of the area of viral attachment to the primary immune cells HIV infects.
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Credit: NIAID VRC
The researchers also determined the atomic-level structure of VRC01 when it is attaching to HIV. This enabled the team to define how the antibody works and to precisely locate where it attaches to the virus. With this knowledge, they have begun to design components of a candidate vaccine that could teach the human immune system to make antibodies similar to VRC01 that might prevent infection by the vast majority of HIV strains worldwide.
NIAID scientists Peter D. Kwong, Ph.D., John R. Mascola, M.D., and Gary J. Nabel, M.D., Ph.D., led the research. A pair of articles about these findings was published July 8 in the online edition of Science.
Finding individual antibodies that can neutralize HIV strains anywhere in the world has been difficult because the virus continuously changes its surface proteins to evade immune system recognition. As a consequence, an enormous number of HIV variants exist worldwide. Even so, scientists have identified a few areas on HIV’s surface that remain nearly constant across all variants. One such area, located on the surface spikes used by HIV to attach to immune system cells and infect them, is called the CD4 binding site. VRC01 and VRC02 block HIV infection by attaching to the CD4 binding site, preventing the virus from latching onto immune cells.
“The discoveries we have made may overcome the limitations that have long stymied antibody-based HIV vaccine design,” says Dr. Kwong.