New Target Found for Potential HIV Vaccine
by
, 05-14-2016 at 04:54 AM (841 Views)
Researchers isolated an antibody from a person infected with HIV that can block the virus from infecting other cells.
Shortly after HIV was identified in 1984 as the cause of AIDS, scientists started working on a vaccine to protect people against the infection.
But HIV is a complex and changeable virus, making a safe and effective vaccine elusive.
Still, the attempt continues.
The latest discovery on this front comes from a team led by scientists at the National Institutes of Health (NIH).
Researchers have discovered an antibody that can bind to a region on HIV and stop it from infecting cells. This antibody also targets an area of the virus that was thought to be invulnerable.
While the discovery has generated excitement, it is tempered by the difficulty researchers have had in the past in outmaneuvering HIV.
“I’m actually sort of excited by just finding something interesting,” Peter Kwong, Ph.D., a senior investigator at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases, said in an interview with Healthline.
“We hope that it will go somewhere. We don’t know, but I do think it’s a promising lead.”
A Surprising New Antibody
In the new study, published online today in the journal Science, researchers examined the blood of a person infected with HIV.
In the blood they found an antibody — a protein made by the immune system — that was able to prevent roughly half of the 208 HIV variations tested from infecting other cells.
Although antibodies produced in the body after HIV infection may stop new infections in the lab, they don’t allow a person’s immune system to rid the body of HIV. That’s because these antibodies are not always effective or develop after infection.
Antibodies target specific areas on a virus or bacteria. The one that the researchers isolated didn’t match any of the known target areas on HIV.
But the antibody did bind to a region on the virus that no one suspected was open to attack.
“This is the first time that a specific epitope — or a very specific region of the protein — has been identified as a neutralizing epitope and can be targeted by antibodies to block HIV entry,” Dr. Michael Root, Ph.D., an associate professor in the Department of Biochemistry and Molecular Biology at Thomas Jefferson University, told Healthline.
New Target Identified
The targeted region is called the fusion peptide.
The fusion peptide helps the HIV membrane fuse with the same element of the cell. This is needed for the virus to infect a cell with its genetic material.
It is part of a larger virus structure called the envelope glycoprotein. This viral machinery binds to a receptor on the target cell and undergoes a series of shape changes that allow the virus to fuse to the target cell.
Scientists have known about the fusion peptide for a long time. But they did not think it was exposed in its pre-fusion shape.
“These machines are sort of like Transformer toys. They go from one shape to a completely different shape,” said Kwong. “It was thought that in the first shape, the fusion peptide would be buried because it’s a pretty hydrophobic, reactive thing.”
Hydrophobic — meaning afraid of water — areas of a virus tend to avoid contact with the surrounding environment by closing themselves off.
Antibodies can only attach to regions that they can reach.
The researchers discovered that the fusion peptide is not as hidden as once believed.
“What we can see in this is that the internal half of [the fusion peptide] — about eight amino acids — is actually exposed and can be recognized by an antibody,” said Kwong.
Waiting to Be Discovered
Researchers don’t know exactly how the new antibody blocks HIV infection, but they suspect it prevents the envelope glycoprotein from going through its shape changes.
“If [the fusion peptide] is locked and bound by an antibody, it can’t do that,” said Kwong. “So it basically prevents the machine from working.”
What makes this discovery promising is that this region seems to be the same in most of the variations of HIV out there.
“It’s nice because that structure is pretty conserved among HIV. So theoretically the virus might have a harder time figuring out ways to become resistant to antibodies that are targeting that region,” said Root. “I say that’s theoretical because the virus has an amazing ability to escape neutralization.”
Some HIV variants are known to exist that the antibody does not neutralize, but these are well understood.
“If we can raise antibodies against the fusion peptide,” said Kwong, “then we should be able to raise antibodies against variants of the fusion peptide.”
Combining these antibodies could neutralize most variations of HIV.
More work is needed to know if this can be turned into an effective vaccine against HIV. This includes years of testing in animals, followed by careful clinical trials in people.
This research, though, shows that promising new antibodies may still be out there waiting to be discovered.
“We’ve found one example of a donor that has made antibodies against the fusion peptide,” said Kwong. “How many other donors are there? People haven’t really been looking in this region [of the virus].
Source: New Target Found for Potential HIV Vaccine