Newly discovered antibodies may boost AIDS vaccine research

Inducing production of the potent HIV neutralizers will be challenge

Scientists have discovered three previously unknown human antibodies that neutralize HIV, two of which target a broad range of HIV strains. The findings, reported online July 8 in two Science papers, come less than a year after another team of researchers discovered two other antibodies that bind to and neutralize HIV.

The discoveries may jump-start AIDS vaccine research. “The path forward isn’t as clear as we’d like it to be, but we are turning a corner, I think,” says David Montefiori, a viral immunologist at Duke University Medical Center in Durham, N.C., who was not involved in the research.

Nearly everyone infected with HIV makes some antibodies to it. But while HIV antibodies have been detected since the 1990s, none has had the properties to serve as a cornerstone around which to build a vaccine.

The newer antibodies might be made of tougher stuff. One in particular, called VRC01, displays potency and broad coverage across HIV strains, says Peter Kwong, a structural biologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Md., who coauthored both new reports.

In the new studies, Kwong and his colleagues collected antibodies from the blood of HIV-infected people. They then tested these antibodies against nearly 200 strains of HIV in the lab to determine how many strains were susceptible to each antibody and how much antibody was needed to neutralize the virus.

VRC01 and its sister antibody VRC02 neutralize 91 percent of HIV strains, the team reports. A third antibody, VRC03, neutralized 57 percent. By comparison, an antibody discovered in the 1990s neutralized only about 40 percent of known HIV strains, and the PG9 and PG16 antibodies unveiled last year neutralized 79 percent and 73 percent of strains.

The findings over the past year “establish a proof of the principle that it’s possible for the body to generate these kinds of antibodies,” Montefiori says. “We haven’t seen anything like what these antibodies can do — not even close.”

Scientists will do well to design an HIV vaccine that elicits the immune system to produce a combination of antibodies, to get an additive effect, Montefiori says.

HIV poses challenges for vaccine design because it mutates frequently. This changing appearance limits immune detection, says Ralph Pantophlet, a vaccine immunologist at Simon Fraser University in Canada. The virus is also camouflaged from the immune system by sugar molecules, he says.

In one of the new reports, the researchers took apart the VRC01 antibody and found that it binds to HIV on a site that the virus needs to latch onto unsuspecting cells and gain entry into them. VRC01 bottles up HIV by mimicking that cell docking station, a receptor protein.

“The size of the antibody keeps the virus from approaching the cell,” Pantophlet says. The bound virus and antibody soon face disposal, he says.

The VRC01 antibody showed up in only one individual and seems to take a few years to appear after infection. Before they can develop a vaccine that induces its production, scientists must first ascertain that the antibody exists in others. The delay in antibody production might be manageable, Kwong says. Vaccinations are commonly given over many months.

The most difficult part may be constructing the vaccine itself, with additives to “wake up the immune system,” Montefiori says.

Kwong says the work will involve manipulating the immune system to produce these antibodies. “The answer is going to be there, and it’s going to be doable,” he says.

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