Doctors have been using a range of antibodies to attack HIV for years, and a new report has revealed yet another weapon in the battle against AIDS: an antibody called 8ANC195.
According to the report, published in the journal Cell, 8ANC195 is a broadly neutralizing antibody (bNAb) capable of latching on to a signature HIV protein and effectively neutralizing the virus.
The signature protein on the surface of the virus, called the envelope spike, can take on different conformations during infection, and 8ANC195 is capable of recognizing these different conformations, making the antibody uniquely effective.
The sequence of HIV infection starts when the virus is exposed to human immune cells known as T cells that carry a certain protein, CD4, on their exterior. Envelope spikes on the exterior of the HIV virus identify and bind to the CD4 proteins, and the spikes go from the “closed” conformation to the “open” conformation when the spike adheres to CD4. The open conformation then allows the HIV virus to put its genetic material inside the host cell, compelling it to become a manufacturer of new viruses that can go on to infect other cells.
A different bNAb
Most identified bNAbs only recognize the spike in the closed conformation, and each bNAb recognizes just one particular target, or epitope, of this protein. Some targets permit a more potent neutralization of the virus, and, therefore, some bNAbs are more efficient against HIV than others. Previous research by the study team had identified 8ANC195 as targeting a different epitope than any other known bNAb.
“We previously were able to define the binding site of this antibody on a subunit of the HIV envelope spike, so in this study we solved the three-dimensional structure of this antibody in complex with the entire spike, and showed in detail exactly how the antibody recognizes the virus,” study author Louise Scharf, a postdoctoral researcher at Caltech, said in a news release.
“Our collaborators at Rockefeller have studied this extensively in animal models, showing that if you administer a combination of these antibodies, you greatly reduce how much of the virus can escape and infect the host,” Scharf says. “So 8ANC195 is one more antibody that we can use therapeutically; it targets a different epitope than other potent antibodies, and it has the advantage of being able to recognize these multiple conformations.”
The study team found that 8ANC195 can also recognize the envelope spike in both the closed conformation and a partially open conformation. They noted that the bNAb could potentially be added to the usual “cocktail” of antibodies given to individuals with HIV.
“In addition to supporting the use of 8ANC195 for therapeutic applications, our structural studies of 8ANC195 have revealed an unanticipated new conformation of the HIV envelope spike that is relevant to understanding the mechanism by which HIV enters host cells and bNAbs inhibit this process,” noted study leader Pamela Bjorkman, professor of biology at Caltech.
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Feature Image: Louise Scharf/Caltech
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