The search for a vaccine against AIDS has been long and fruitless — mostly because the virus mutates so fast. As is well known, flu vaccines have to be reformulated every year because influenza viruses mutate so steadily. But the human immunodeficiency virus, which causes
AIDS, mutates as much in a single day as flu virus does in a year, presenting
scientists with an almost insurmountable challenge.
This month, South African researchers announced that they had found a
vulnerable spot on the virus’s outer shell that might present a good vaccine
target, and that they had also learned, for the first time, at what stage of an
infection it develops. They found only two women whose virus had the
vulnerability — and it wasn’t the same virus that first infected them, but a
mutant that developed a few months later.
The research, published by Nature Medicine on Oct. 21, was praised as “very interesting” by
several AIDS experts. “It’s a combination of good science and ‘Boy, did we get
lucky,’ ” said Dr. Anthony S. Fauci, director of the National Institute of
Allergy and Infectious Diseases. “They had all these blood samples and virus
samples.” The researchers, led by Dr. Salim Abdool Karim, president of South
Africa’s Medical Research Council and best known for pioneering work on vaginal
microbicides, screened hundreds of blood samples given at regular intervals by
79 women who had been in earlier clinical trials at his Durban clinic and had
become infected during the trials.
“What we have that’s unique,” Dr. Karim said, “is that for the first
time, we understand how a person can make broadly neutralizing antibodies.”
The virus’s vulnerable spot — open to antibody attack — was created when a
sugarlike surface compound called a glycan shifted positions. Antibodies are Y-shaped proteins produced by the immune system that
attach to a virus and block its outer receptors — sort of the way sweater fuzz
attaches to Velcro and renders it unsticky.
There are many strains of H.I.V., and no known antibody incapacitates
all of them. But in the last few years, several teams of scientists have
isolated about a dozen that each can shut down up to 80 percent of all virus
strains. These are said to be “broadly neutralizing.” Less than 20 percent of
all patients naturally develop such antibodies in their blood, and even those
who do aren’t fully protected. One of the women whose blood was crucial to Dr.
Karim’s study has died of AIDS-related tuberculosis, and the other is on
antiretroviral drugs.
Nonetheless, experts hope it will eventually be possible to manufacture
cocktails with large doses of several kinds of antibodies to treat patients —
or even to induce the immune system to make those particular antibodies, which
would amount to a vaccine. But that will take more work, and more luck. Dr.
John P. Moore, an AIDS researcher at Weill Cornell Medical School, called the
South African paper “good solid science, but not enough to know if you have the
right target.” “It’s like looking at a castle and saying: ‘I can see a weak
point, but I don’t know what kind of battering ram to get,’ ” he added.
Normally, H.I.V. repels antibodies by mutating its Velcro hooks into
different shapes. But some spots on the viral shell don’t change shape easily.
Scientists from the National Institute for Communicable Diseases in South
Africa and universities in KwaZulu/Natal, Cape Town and North Carolina, as well
as from Harvard, screened multiple blood samples looking for previously known
antibodies. They found them in the two women, and noted how long into their
infections those antibodies appeared — around six months, it turned out, after
their infections were first detected.
Then the scientists looked to see what exactly had changed in the virus
circulating in their blood at that time. They found that a sugarlike glycan had
moved from Position 334 to Position 332 on one of the lumpy spikes that stud
the virus. That tiny change allows the antibody to attach and alert the body
that the whole round virus is an invader, Dr. Karim said. Antibodies neutralize
viruses by blocking their receptors and by attracting white blood cells that will
engulf the virus.
Most of the work was done by South Africans and paid for by the South
African government, Dr. Karim said proudly, although additional money came from
the United States National Institutes of Health and the Bill & Melinda
Gates Foundation. Dr. Karim, who also teaches at Columbia University in New
York, particularly praised one local researcher, Penny L. Moore of the National
Health Laboratory Service in Johannesburg. “She’s one of our up-and-coming
stars,” he said. “Old fogies like myself are quickly becoming redundant.”
NY Times
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