NEW IDENTIFYING ANTIBODY NEUTRALIZED HIV VIRUSES
A team of researchers led by Dr. Mark Connors of NIH’s National Institute of Allergy and Infectious Diseases has identified an antibody from an HIV-infected person that neutralized 98% of HIV strains tested, including 16 of 20 strains resistant to other members of its class.
Identifying broadly neutralizing antibodies against human immunodeficiency virus (HIV) has been difficult because the virus rapidly changes its surface proteins to evade recognition by the immune system.
In 2010, researchers discovered an antibody called VRC01 that can stop up to 90% of HIV strains from infecting human cells.
Like VRC01, the newly identified antibody 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.
“The remarkable breadth and potency of this antibody, called N6, make it an attractive candidate for further development to potentially treat or prevent HIV infection,” Dr. Connors and co-authors said.
They also tracked the evolution of N6 over time to understand how it developed the ability to potently neutralize nearly all HIV strains.
The team’s findings, published in the Nov. 15 issue of the journal Immunity, 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.
The results suggest that N6 could pose advantages over VRC01, which currently is being assessed as intravenous infusions in clinical trials to see if it can safely prevent HIV infection in humans.
Due to its potency, N6 may offer stronger and more durable prevention and treatment benefits, 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.
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Jinghe Huang et al. 2016. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth. Immunity45 (5): 1108-1121; doi: 10.1016/j.immuni.2016.10.027
