First Time, AIDS Vaccine Shows Some Success
September 24, 2009
The New
York Times
For
First Time, AIDS Vaccine Shows Some Success
By
DONALD G. McNEIL Jr.
Click here to read the article online.
A new
AIDS vaccine tested on more than 16,000 volunteers in Thailand has protected a
significant minority against infection, the first time any vaccine against the
disease has even partly succeeded in a clinical trial.
Scientists
said they were delighted but puzzled by the result. The vaccine — a combination
of two genetically engineered vaccines, neither of which had worked before in
humans — protected too few people to be declared an unqualified success. And the
researchers do not know why it worked.
“I
don’t want to use a word like ‘breakthrough,’ but I don’t think there’s any
doubt that this is a very important result,” said Dr. Anthony S. Fauci, director
of the National Institute of Allergy and Infectious Diseases, which is one of
the trial’s backers.
“For
more than 20 years now, vaccine trials have essentially been failures,” he went
on. “Now it’s like we were groping down an unlit path, and a door has been
opened. We can start asking some very important
questions.”
Results
of the trial of the vaccine, known as RV 144, were released at 2 a.m. Eastern
time Thursday in Thailand by the partners that ran the trial, by far the largest
of an AIDS vaccine: the United States Army, the Thai Ministry of Public Health,
Dr. Fauci’s institute, and the patent-holders in the two parts of the vaccine,
Sanofi-Pasteur and Global Solutions for Infectious
Diseases.
Col.
Jerome H. Kim, a physician who is manager of the army’s H.I.V. vaccine program,
said half the 16,402 volunteers were given six doses of two vaccines in 2006 and
half were given placebos. They then got regular tests for the AIDS virus for
three years. Of those who got placebos, 74 became infected, while only 51 of
those who got the vaccines did.
Although
the difference was small, Dr. Kim said it was statistically significant and
meant the vaccine was 31.2 percent effective.
Dr.
Fauci said that scientists would seldom consider licensing a vaccine less than
70 or 80 percent effective, but he added, “If you have a product that’s even a
little bit protective, you want to look at the blood samples and figure out what
particular response was effective and direct research from
there.”
The
most confusing aspect of the trial, Dr. Kim said, was that everyone who did
become infected developed roughly the same amount of virus in their blood
whether they got the vaccine or a placebo.
Normally,
any vaccine that gives only partial protection — a mismatched flu shot, for
example — at least lowers the viral load.
That
suggests that RV 144 does not produce neutralizing antibodies, as most vaccines
do, Dr. Fauci said. Antibodies are long Y-shaped proteins formed by the body
that clump onto invading viruses, blocking the surface spikes with which they
attach to cells and flagging them for destruction.
Instead,
he theorized, it might produce “binding antibodies,” which latch onto and
empower effector cells, a type of white blood cell attacking the
virus.
Whatever
the vaccine does, he said, it does not seem to mimic the defenses of the rare
individuals known to AIDS doctors as “long-term nonprogressors,” who do not get
sick even though they are infected. They have low viral loads because they block
reproduction in some way that is still mysterious.
“If we
knew what immune response did it, we’d be able to be a lot more efficient in
targeting it,” Dr. Kim said.
Also,
the RV 144 tested in Thailand was designed to combat the most common strain of
the virus circulating in Southeast Asia. Different strains circulate in Africa,
the United States and elsewhere, and it is not clear that the vaccine would have
similar results, even in modified form.
The
thousands of Thais chosen were a cross-section of the Thai young adult
population, not just high-risk groups like drug injectors or sex workers, Dr.
Kim said.
One of
the substances that were combined to make RV 144 is Alvac-HIV, from
Sanofi-Pasteur, a canarypox virus with three AIDS virus genes grafted onto it.
Variations of Alvac were tested in France, Thailand, Uganda and the United
States; it was found safe but generated little immune
response.
The
other, Aidsvax, was originally made by Genentech and is an engineered version of
a protein found on the surface of the AIDS virus; it is grown in a broth of
hamster ovary cells.
It was
tested in Thai drug users in 2003 and also in gay men in North America and
Europe; it did not protect them against infection, and Genentech spun off the
rights to develop the vaccine.
In
2007, two trials of a Merck vaccine in about 4,000 people were stopped early; it
not only failed to work but for some men seemed to increase the risk of
infection.
Combining
Alvac and Aidsvax was a hunch by scientists: If one was designed to create
antibodies and the other to alert white blood cells, might they work together
even if neither worked alone?
Mitchell
Warren, executive director of AVAC, the AIDS Vaccine Advocacy Coalition, which
pushes for vaccines and other forms of prevention, was enthusiastic about the
trial data.
“Wow,”
he said. “This is a hugely exciting and, frankly, unexpected result. It changes
our thinking in ways we hadn’t anticipated.”
“We
often talk about whether a vaccine is even possible,” he added. “This is not the
vaccine that ends the epidemic and says, ‘O.K., let’s move on to something
else.’ But it’s a fabulous new step that takes us in a new
direction.”
Mr.
Warren said the finding showed the need for large human trials, expensive as
they are. Studies in mice and monkeys have not been good at predicting what
would work in people, and small human trials in which researchers test results
by looking for antibodies in blood have limited value.
Dr.
Fauci agreed.
“This
is not the endgame,” he said. “This is the beginning.”
***
