Good News From the HIV Vaccine Trial: The Success That Came from Failure
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Posted Thursday, September 24, 2009 3:30 PM
Newsweek
by Mary Carmichael
Last year the prospects for an HIV vaccine looked so bleak that some scientists began to talk
about calling off the search all together. But today, the AIDS research community is re-
energized—and surprised—by new data showing for the first time that a vaccine can partly stop
transmission of the virus in humans.
Many in the community had not expected the vaccine to succeed, and they still don’t understand
exactly how it works. It’s “a humbling reminder of how little we actually know,” says Anthony
Fauci, director of the National Institute of Allergy and Infectious Diseases, which helped fund
the trial. But it’s also the best lead the field has produced in a decade—and that means that
instead of stopping the search for a fully effective AIDS vaccine, it’s time to rev things up.
The vaccine, which was tested in Thailand by a collaboration of world health organizations, cut
down on transmission of the virus by almost a third. (8,000 volunteers received the vaccine, and
51 of them became infected afterwards; 8,000 more received a placebo, and a higher number—
74—became infected.) The vaccine’s 31 percent success rate falls far short of the 80 percent that
public health officials like to see before licensing a product for wide use. On the other hand, it’s
much better than zero percent effective, and that’s the outcome a lot of people were expecting.
“If you had asked me to bet money last week, this was probably the least likely result I would
have bet on,” says Mitchell Warren, executive director of AVAC, the Aids Vaccine Advocacy
Coalition. The trial sounded so futile to some that one advocacy group called for its end in 2005,
saying it was “squandering public goodwill and scarce research funds to boot.”
Why were people so pessimistic about the Thai trial? The AIDS vaccine field is littered with
failed experiments, and this one had some precedents that were especially discouraging. The
vaccine is made of two parts, neither of which had worked in previous human trials. One of the
two components, a formulation called AIDSVAX, flopped in a large trial in 2003 when given on
its own. AIDSVAX caused the human body to make antibodies against HIV, but the antibodies
were never a close enough match to latch onto and attack the fast-mutating virus.
After that disappointment, researchers turned away from the antibody approach and focused on a
vaccine that tried to deploy another facet of the immune system, the body’s T cells. A Merck
vaccine based on this concept of “cellular immunity” showed real potential in monkeys, but it
didn’t work in humans—and it may have even increased the risk of infection in some patients.
Soon after the news broke, some scientists began to wonder if the entire search for a vaccine was
futile.
By that time, though, the Thai trial was already underway. Unlike the AIDSVAX and Merck
trials, it was testing a new double-barreled strategy against the virus—the “prime boost” method,
which conditions the body to attack HIV and then bolsters the immune system’s ongoing
response. How exactly it might do that is unclear—no other vaccine works that way—but
investigators who have seen the Thai data have a theory. The vaccine may first cause the body to
produce an unusual class of antibodies that can pump up the power of immune cells called “T
effectors.” These cells are then able to attack the virus before it can establish a home in the body.
That means the major debate among AIDS vaccine researchers—should we use antibodies, or
should we use T cells?— is now somewhat moot. It turns out we may need both.
There’s a lot more research to do on the Thai vaccine, then—starting with a detailed look at the
31 percent of people who were protected against the virus. Scientists need to know what exactly
was shielding them from infection and whether that shield remains strong in the long term.
They’ll also need to follow the unlucky 69 percent who did get infected during the trial to see if
they fare any better, health-wise, than people who never received a vaccine. They’ll need to
design more trials of the Thai vaccine, which has only been tested on the B and E strains of HIV
that circulate in Southeast Asia, not the C strain that dominates in Africa. Most of all, of course,
they’ll need to figure out a way to increase the vaccine’s effectiveness from 31 percent to
something much higher. The planning is likely to start in October, when the more results from
the trial are released at an international conference in Paris.
Research on related strategies will continue as well; today alone, two new initiatives are being
launched to study antibody-based approaches. One, at the Scripps Research Institute, is based on
groundbreaking research published just three weeks ago in the journal Science, describing two
newly discovered potent antibodies against HIV. The other, spearheaded by a foundation called
Covalent Immunology, involves chemical manipulation of the same AIDSVAX formulation
used in Thailand; it may make it even more powerful.
Just a few hours after the Thai vaccine researchers announced their success, an advocacy group
that had criticized vaccine research for siphoning money from treatment and on-the-ground
prevention programs sent out a press release. Instead of relenting, it was retrenching. “News of a
successful HIV AIDS vaccine trial is welcome,” read the statement from ActionAid, “but
treating existing infections and fighting the underlying epidemic of violence against women
remain more important priorities.” The sentiment is understandable. The Thai vaccine works in
only a third of people while treatment works for many more; a truly effective vaccine is still
years (and probably billions of dollars) in the making while treatment is available now. And
stopping sexual assault obviously has benefits for women far beyond preventing AIDS.
Ultimately, though, a vaccine is the only thing that’s going to wipe out HIV. Yes, there are drugs
and public health programs in place today, but 3.1 million people still die of AIDS every year, a
fifth of them children. “At the end of the day, nobody’s ever completely controlled a major viral
epidemic without a vaccine,” says Seth Berkley, CEO of the International AIDS Vaccine
Initiative. “And that is the goal – to end this pandemic. People are talking about AIDS as a
chronic disease. We don’t want it as a chronic disease. We want it gone.” At least now there’s a
glimmer of hope that someday it will be.
http://blog.newsweek.com/blogs/thehumancondition/archive/2009/09/24/good-news-from-the-
hiv-vaccine-trial-the-maybe-cure-that-almost-wasn-t.aspx
