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Findings May Hold Value for Future HIV-1 Vaccine Design

Last Updated: July 12, 2010.

Three previously unknown monoclonal antibodies can neutralize most circulating HIV-1 isolates, and one of these partially imitates the interaction of the CD4 receptor with the viral envelope protein but focuses on a site consistent between strains, allowing for broad neutralization, according to the results of two studies published online July 8 in Science.

MONDAY, July 12 (HealthDay News) -- Three previously unknown monoclonal antibodies can neutralize most circulating HIV-1 isolates, and one of these partially imitates the interaction of the CD4 receptor with the viral envelope protein but focuses on a site consistent between strains, allowing for broad neutralization, according to the results of two studies published online July 8 in Science.

In the first study, Xueling Wu, Ph.D., of the National Institutes of Health (NIH) in Bethesda, Md., and colleagues write that they developed antigenically resurfaced glycoproteins that were specific for the conserved CD4 receptor binding site. They then identified sera with neutralizing antibodies (NAbs) to the CD4-binding site and isolated B cells from an individual with HIV-1 whose sera contained broadly reactive NAbs. After expressing immunoglobulin genes from individual cells, the researchers found three monoclonal antibodies that included two somatic variants that neutralized more than 90 percent of circulating HIV-1 isolates.

In the second study, Tongqing Zhou, Ph.D., also of the NIH, and colleagues assessed the crystal structure of one of these antibodies -- VRC01 -- in complex with an HIV-1 gp120 core. They found that, to an extent, VRC01 mimics CD4 interaction with gp120. However, they write that it focuses on the vulnerable site of initial CD4 attachment, allowing it to overcome issues that reduce the neutralization effect of most CD4-binding-site antibodies.

"To achieve this recognition, VRC01 contacts gp120 mainly through Vgene-derived regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies," Zhou and colleagues conclude.

Several co-authors of the first study are investors in a provisional patent application (filed by the NIH) on monoclonal antibodies discussed in the study.

Abstract - Wu
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Abstract - Zhou
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