You can’t defeat what you can’t identify. That’s part of the human body’s problem with HIV–a virus that mutates constantly. Most antibodies can identify, latch onto, and neutralize only certain variants of the virus, or none at all. But two new studies published in Science yesterday point to two antibodies that almost always hits their targets--neutralizing some 90 percent of the most common HIV strains.
Scientists hope to eventually use their knowledge of these antibodies to develop a vaccine, but this is not an easy task.
“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. [Science News]
But first, how did they find these antibodies?
Step 1: Learning from a Survivor
Researchers at the National Institute of Allergy and Infectious Diseases looked at the blood of a 60-year-old African American man who had survived with HIV for 20 years.
The HIV antibodies were discovered in the cells of a 60-year-old African-American gay man, known in the scientific literature as Donor 45, whose body made the antibodies naturally…. Donor 45’s antibodies didn’t protect him from contracting HIV. That is likely because the virus had already taken hold before his body produced the antibodies. He is still alive, and when his blood was drawn, he had been living with HIV for 20 years. [Wall Street Journal]
Something about Donor 45’s antibodies were keeping the virus at bay or, more specifically, keeping it from binding with certain white blood cells to infect and destroy them.
Step 2: Trolling for Antibodies
Researchers suspected that the antibodies were manipulating a piece of the virus that remained relatively the same despite the virus’s overall shape-shifting. A prime suspect were the tiny “spikes” (see Wall Street Journal illustration) where the virus attached to white blood cells.
The researchers used a probe that was something like one of these spikes to see what antibodies they could reel in.
The team screened 25 million antibody-producing white blood cells, called B cells, from 15 people with HIV-1 [the most common strain of the virus], searching for those that bound to their probe. Only 29 cells fit the bill. From those, the researchers isolated three broadly neutralizing antibodies. [Nature News]
Of the “broadly neutralizing” antibodies, two could neutralize 90 percent of the HIV-1 mutations.
Step 3: Antibodies for Everyone
Donor 45 contracted HIV because his body produced the antibodies after he was already infected, but what if he had been prepared with the antibodies before the virus attacked? Perhaps he then could have thwarted infection all together. That’s the ideal case for a vaccine.
“I am more optimistic about an AIDS vaccine at this point in time than I have been probably in the last 10 years,” Dr. Gary Nabel of the National Institute of Allergy and Infectious Diseases, who led the study, said in a telephone interview…. “This is an antibody that evolved after the fact. That is part of the problem we have in dealing with HIV — once a person becomes infected, the virus always gets ahead of the immune system,” Nabel said.”What we are trying to do with a vaccine is get ahead of the virus.” [Reuters]
Getting ahead isn’t easy. For one, the antibodies don’t seem to work the moment the B cells start producing them–the antibodies have to mutate and mature themselves to become effective virus-blockers. These broad neutralizing antibodies have an unusually large number of mutations.
“Antibodies are like people: every single one is unusual in its own specific way,” says Peter Kwong, a structural biologist at the Vaccine Research Center, and a co-author on both papers. “These antibodies are freaks of nature.” [Nature News]
Getting the body to produce these antibodies naturally in this mature state, again, would be ideal–though difficult given their complexity. Researchers are also looking into treatments based on applying pre-made antibodies directly.
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Image: Wikimedia / HIV Budding