HIV Prevention and Treatment May Be All in the Antibodies

There are many moving parts when it comes to the immunodeficiency virus (HIV), and focusing on the body’s natural antibodies may be just what the doctor ordered.

A small percentage of patients with HIV are elite controllers, meaning they have an undetectable viral load because their bodies naturally control the virus. This occurs, in part, as a result broadly neutralizing antibodies (bNAbs). It is suspected that these proteins protect healthy cells by recognizing the envelope spike — a protein found on the surface HIV strains – and then neutralizing it. Previous research has shown that mimicking this process could lead to an effective HIV vaccine. Now, researchers from Caltech have taken the analysis a step further by pinpointing one specific bNAb that may be the key to infection prevention.

“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 three-dimensional structure of this antibody in complex with the entire spike, and showed in detail exactly how the antibody recognizes the virus,” first author Louise Scharf, a postdoctoral scholar in Pamela Bjorkman’s, PhD, laboratory, said in a news release.

Every bNAb targets the envelope spike, however, each one has a specific target which makes some more effective against HIV than others. In 2014, the team found the bNAb, 8ANC195, in the blood of elite controllers. The latest research published in Cell takes a deeper look at the function of 8ANC195 using X-ray crystallography and electron microscopy.

The envelope spike can either be in an open or closed conformation, but most bNAbs are known to only recognize the closed. However, the researchers found that 8ANC195 can recognize the protein in closed and partially open conformation.

Furthermore, most HIV infections occur when the virus latches on to T cells and infects the cells (the envelope spike would typically be in closed conformation in this situation). Most bNAbs could neutralize this process, however, when HIV spreads by directly moving from cell-to-cell, it is an open conformation. The team discovered that 8ANC195 was able to recognize this envelope spike and attach to it.

“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,” Scharf explained.

The researchers hypothesize that these findings could be worked into an antibody treatment that would inhibit the virus.

“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 confirmed.