[Ip-health] New York Times: For First Time, AIDS Vaccine Shows Some Success

[Thiru Balasubramaniam]

September 25, 2009
For First Time, AIDS Vaccine Shows Some Success
By DONALD G. McNEIL Jr.

Scientists said Thursday that a new AIDS vaccine, the first ever
declared to protect a significant minority of humans against the
disease, would be studied to answer two fundamental questions: why it
worked in some people but not in others, and why those infected
despite vaccination got no benefit at all.

The vaccine =97 known as RV 144, a combination of two genetically
engineered vaccines, neither of which had worked before in humans =97
was declared a qualified success after a six-year clinical trial on
more than 16,000 volunteers in Thailand. Those who were vaccinated
became infected at a rate nearly one-third lower than the others, the
sponsors said Thursday morning.

=93I don=92t want to use a word like =91breakthrough,=92 but I don=92t thin=
k
there=92s any doubt that this is a very important result,=94 said Dr.
Anthony S. Fauci, the director of the National Institute of Allergy
and Infectious Diseases, which is one of the trial=92s backers.

=93For more than 20 years now, vaccine trials have essentially been
failures,=94 Dr. Fauci said. =93Now it=92s like we were groping down an
unlit path, and a door has been opened. We can start asking some very
important questions.=94

It will still, however, take years of work before a vaccine that could
end the epidemic, which has killed about 25 million people, can even
be contemplated.

=93We often talk about whether a vaccine is even possible,=94 said
Mitchell Warren, the executive director of the AIDS Vaccine Advocacy
Coalition, or AVAC. =93This is not the vaccine that ends the epidemic
and says, =91O.K., let=92s move on to something else.=92 But it=92s a fabul=
ous
new step that takes us in a new direction.=94

In which direction is still unknown. No one =97 including the
researchers from the United States Army, the National Institutes of
Health, the Thai Ministry of Public Health and two vaccine companies
that tested the vaccine =97 knows why the vaccine gave even its weak
indicator of success.

Experts generally disdain vaccines that do not protect at least 70 to
80 percent of those getting them. And this vaccine did not lower the
viral loads of people who were vaccinated but caught the virus anyway,
which was baffling because even mismatched vaccines usually do that.

Simply repeating the trial to confirm the results would be pointless,
experts agreed.

The trial, the largest AIDS vaccine trial in history, cost $105
million and followed 16,402 Thai volunteers.

The men and women ages 18 to 30 were recruited from two provinces
southeast of the capital, Bangkok, from the general population rather
than from high-risk groups like drug injectors or sex workers. Half
got six doses of two different vaccines; half were given placebos.

For ethical reasons, all were offered condoms, taught how to avoid
infection and promised lifelong antiretroviral treatment if they got
AIDS. They were then regularly tested for three years; 74 of those who
got placebos became infected, but only 51 of those who got the
vaccines did.

Although the difference was a mere 23 people, Col. Jerome H. Kim, a
physician and the manager of the Army=92s H.I.V. vaccine program, said
it was statistically significant and meant that the vaccine was 31.2
percent effective.

The results were surprising because both vaccines, one from the French
company Sanofi-Aventis and one developed by Genentech but now licensed
to Global Solutions for Infectious Diseases, a nonprofit health group,
had failed when used individually.

=93This came out of the blue,=94 said Chris Viehbacher, Sanofi=92s chief
executive. Even 31 percent protection =93was at least twice as good as
our own internal experts were predicting,=94 he added.

In 2004, there was so much skepticism about the trial just after it
began that 22 top AIDS researchers published an editorial in Science
magazine suggesting that it was a waste of money.

One conclusion from the surprising result, said Alan Bernstein, head
of the Global HIV Vaccine Enterprise, an alliance of organizations
pursuing a vaccine, =93is that we=92re not doing enough work in humans.=94

Instead of going back to mice or monkeys, he said, different new
variants on the two vaccines could be tried on a few hundred people in
several countries.

This vaccine was designed to combat the most common strain of the
virus in Southeast Asia, so it would have to be modified for the
strains circulating in Africa and the United States.

Sanofi=92s vaccine, Alvac-HIV, is a canarypox virus with three AIDS
virus genes grafted onto it. Variations of it were tested in several
countries; it was safe but not protective. The other vaccine, Aidsvax,
was originally made by Genentech and contains 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 in gay men in
North America and Europe but failed.

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 also seemed
to increase the risk of infection.

Combining Alvac and Aidsvax was simply a hunch: if one was designed to
create antibodies and the other to alert white blood cells, might they
work together?

One puzzling result =97 those who became infected had as much virus in
their blood whether they got the vaccine or a placebo =97 suggests that
RV 144 does not produce neutralizing antibodies, as most vaccines do,
Dr. Fauci said. Antibodies are 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 =93binding antibodies,=94 which
latch onto and empower effector cells, a type of white blood cell
attacking the virus. Therefore, he said, it might make sense to screen
all the stored Thai blood samples for binding antibodies.

=93The humbling prospect of this,=94 he said, =93is that we may not even be
measuring the critical parameter. It may be something you don=92t
normally associate with protection.=94

Dr. Lawrence Corey, the principal investigator for the HIV Vaccine
Trials Network, who was not part of the RV 144 trial, said new work on
weakened versions of the smallpox vaccine had produced better pox
=93spines=94 that could be substituted for the canarypox. New trials, he
added, could be faster and smaller if they were done in African
countries where AIDS is more common than in Thailand.

------------------------------------------------------------


Thiru Balasubramaniam
Geneva Representative
Knowledge Ecology International (KEI)
thiru@keionline.org


Tel: +41 22 791 6727
Mobile: +41 76 508 0997