NIH says it has identified an antibody capable of neutralizing almost all HIV strains

Antibody N6 could have advantages over VRC01, which is currently in trials to assess use as intravenous infusion to prevent HIV infection in humans

Jeffrey Bouley
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BETHESDA, Md.—The human immunodeficiency virus (HIV) is a cagey thing, having shown an aptitude for adapting to fight off many therapies over the years. This has made the search for broadly neutralizing antibodies against HIV a challenging one, given that virus is so adept at changing its surface proteins to evade recognition by the immune system. In 2010, researchers at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID)—a component of the U.S. National Institutes of Health (NIH)—had a potential breakthrough with an antibody called VRC01 that can stop as many as 90 percent of HIV strains from infecting human cells.
 
VRC01 is currently is being assessed as intravenous infusions in clinical trials to see if it can safely prevent HIV infection in humans.
 
But there may be a new contender in the battle against HIV with more potential.
 
Scientists at the VRC say they have identified an antibody—dubbed N6—from an HIV-infected person that potently neutralized 98 percent of HIV isolates tested, including 16 of 20 strains resistant to other antibodies of the same class. Commenting on the “remarkable breadth and potency of this antibody”—as NIAID puts it—the researchers not unsurprisingly say that N6 is an attractive candidate for further development to potentially treat or prevent HIV infection.
 
The scientists, led by NIAID’s Dr. Mark Connors, also tracked the evolution of N6 over time to understand how it developed the ability to potently neutralize nearly all HIV strains. This information will “help inform the design of vaccines to elicit such broadly neutralizing antibodies,” NIAID notes.
 
Like VRC01, N6 blocks infection by binding to a part of the HIV envelope called the CD4 binding site, preventing the virus from attaching itself to immune cells.
 
Findings from the current study showed that N6 evolved a unique mode of binding that depends less on a variable area of the HIV envelope known as the V5 region and focuses more on conserved regions, which change relatively little among HIV strains. This allows N6 to tolerate changes in the HIV envelope, including the attachment of sugars in the V5 region, a major mechanism by which HIV develops resistance to other VRC01-class antibodies.
 
As the abstract to their paper—titled “Identification of a CD4-binding site antibody to HIV that evolved near-pan neutralization breadth” and appearing in the Nov. 15 issue of Immunity—notes: “N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permitted it to avoid steric clashes with glycans, which is a common mechanism of resistance. Thus, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis.”
 
Due to its potency, N6 may offer stronger and more durable prevention and treatment benefits than VRC01, and researchers may be able to administer it subcutaneously (into the fat under the skin) rather than intravenously. In addition, its ability to neutralize nearly all HIV strains would be advantageous for both prevention and treatment strategies, NIAID notes.

Jeffrey Bouley

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