Study points to possible path to AIDS vaccine
- Article by: DONALD G. McNEIL Jr.
- New York Times
- April 3, 2013 - 8:02 PM
In what may be an important step toward a long-elusive AIDS vaccine, U.S. researchers have minutely tracked one individual’s powerful immune response to the virus to see how a series of mutations led to an antibody that can defeat many HIV strains. A vaccine still remains far off, but the research lighted up one complex path that may someday be followed to that distant goal.
Thirty-four million people globally are living with HIV, and 2.5 million are newly infected each year, 50,000 of them in the United States.
“The beauty of this is that it’s a big clue as to the sequential steps the virus and the antibody take as they evolve,” said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Disease, which financed the research.
The study was led by scientists at Duke University and also drew in researchers from Columbia, Stanford, the University of Pennsylvania and elsewhere. It was published online Wednesday in the journal Nature.
Scientists have so far failed to produce an AIDS vaccine because HIV mutates so rapidly. Influenza viruses mutate so often that flu shots must be reformulated every year; HIV mutates in one day as much as flu viruses do in a year.
The study analyzed many sequential samples of the blood of one African man from shortly after he was infected until about two years later, when he started to produce “broadly neutralizing antibodies.”
Antibodies are Y-shaped proteins that neutralize virus particles by grabbing onto all the surface receptors they use to attach to cells. The antibodies the patient eventually evolved were called “broadly neutralizing” because they were able to jam up about 55 percent of all known HIV strains.
Scientists have been isolating broadly neutralizing antibodies for several years now, and more than a dozen have been found.
About 20 percent of all HIV carriers eventually produce broadly neutralizing antibodies, Fauci said. But that usually happens only after they have been infected for between two and four years, and by that time the powerful antibodies can’t save them because they are overwhelmed with so much mutating virus.
In theory, if such antibodies could be cloned in bulk, a cocktail of enough variants to match all known HIV strains could be given to newly infected patients. That is the equivalent of an immune globulin shot, which was once the only treatment for some diseases, such as hepatitis.
But it would be very expensive, and the treatment would have to be given for life. And antiretroviral drugs, which cost pennies to make, do the same thing: prevent the virus from replicating.
However, if a healthy patient could be given a vaccine that would induce his own white blood cells to produce the same cocktail of antibodies, they might knock out any infection that the patient got later.
‘A road map’
Because the cells that produce antibodies have to go through up to 100 mutations before they make broadly neutralizing ones, Fauci said, a vaccine to induce that would require many shots, given month after month, to “push” the cells through those mutations. Whether that is possible, let along financially practical, remains to be seen.
Other HIV vaccine experts reacted cautiously to the research, acknowledging that it was first-rate work by a large group of talented researchers, but hedging on its practical implications.
Dr. Louis J. Picker, an HIV vaccine specialist at Oregon Health & Science University, described the work as “a road map to vaccine development, yes — but it’s like one of those maps of the world from the year 1400. We still don’t know how to turn this into a vaccine.”
Dr. Joseph McCune III, head of experimental medicine at the University of California, San Francisco, called it “clarifying science, with a lot of data I hadn’t seen before.”
But he said it was not clear whether one patient’s immune process could be applied to others. “Eighty percent of all patients don’t create broadly neutralizing antibodies,” he said. “What do we do for them? Do we know how protective this strategy is against new infections? And would we have to tailor-make batches of vaccine for people with different backgrounds?”
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