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http://washingtonpost.com/wp-dyn/articles/A10859-2001May10.html

AIDS Vaccine Hopes Rise From Africa

By Karl Vick
Washington Post Foreign Service
Friday, May 11, 2001; Page A01


NAIROBI -- No one knows how many of the perhaps 20,000 men who came to
Salome Kokutona for sex in the last two decades carried the AIDS virus. In
the early days it might have been 1 in 10; lately, more like 1 in 3.

But to scientists nursing fresh hope for a vaccine against HIV, the more
relevant statistic is the number of men who risked contracting the virus
from Kokutona: zero. In a prostitution career that has followed the terrible
arc of the AIDS pandemic in Africa, Kokutona has never been infected,
despite thousands of episodes of unprotected intercourse.

The natural resistance displayed by Kokutona, 42, was also documented in
more than 100 other Nairobi prostitutes. By studying their blood, scientists
in England and Kenya have concocted the first experimental vaccine expressly
intended for Africa -- and at least a hope for safeguarding the lives of the
95 percent of Africans not infected with the human immunodeficiency virus
(HIV), which causes AIDS.

The first, most tentative phase of clinical trials now underway in Kenya
shows promise. In Nairobi residents who are considered at low risk of
contracting HIV, the vaccine appears to stimulate the same immunologic
response seen so strikingly in the sex workers: elevated levels of a
component of the human immune system known as cytotoxic T-lymphocyte cells,
the "killer T-cells" that fight the virus most effectively.

The road to an effective AIDS vaccine is littered with the wreckage of
promising but ultimately failed candidates. To date, more than 30 potential
vaccines have been tested, mainly in the United States and Thailand, and
while some looked promising in early testing, they eventually proved
ineffective or only partially effective.

But given the world's scant investment in AIDS vaccine research, and the
tardiness of its focus on sub-Saharan Africa, any breakthrough would qualify
as a stroke of luck nearly as profound as a Kenyan prostitute finding
herself alive and well 20 years into the pandemic.

Debate over how best to fight AIDS is often cast as competition between
finding ways to treat those with HIV and trying to prevent infection in the
first place.The emergence in the mid-1990s of anti-retroviral medicines,
which prolong the lives of people infected with HIV, sparked an emphasis on
treatment, driven largely by the clout of the West's infected population and
the pharmaceutical industry's desire for marketable products. At that time,
research into vaccines -- the ultimate prevention measure -- accounted for
just 1 percent of worldwide spending on AIDS. The rapid spread of AIDS in
Africa was hardly on anyone's agenda.

Now that industrialized countries have become focused on AIDS in Africa,
home to 25 million of the estimated 36 million people infected with HIV, the
history of this debate is being repeated. What U.N. Secretary General Kofi
Annan calls "a worldwide revolt of public opinion" has driven drug prices
down sharply, meaning that some governments and aid groups may be able to
provide them to some of Africa's afflicted poor. But what Africa still needs
most, according to public health specialists, is a vaccine.

"They've found the problem but have focused on the wrong answer," said Frank
Plummer, the Canadian researcher who first recorded the immunity among
Nairobi's sex workers. "I'm all for treatment, but focusing on treatment as
the solution is not going to solve this."

Nevertheless, health advocates see great opportunities in Annan's bid for a
"war chest" of $7 billion to $10 billion annually to battle AIDS in the
developing world. If the surge to provide treatment means building Africa a
health care infrastructure -- rural clinics, urban laboratories -- the
benefit will not only ease the suffering from AIDS, but fundamentally
improve basic health on a continent plagued by countless diseases.

But that will take time, and time equals lives. According to U.N. estimates,
15,000 people worldwide are infected with HIV each day. Almost every one of
the 25 million Africans who now carry the virus contracted it during the
years since Western science turned its attention away from finding a
vaccine.

"We lost a lot of time," said Seth Berkley, president of the International
AIDS Vaccine Initiative, a nonprofit consortium established to reinvigorate
the vaccine effort. "We probably lost a decade."

The New York-based group has proposed fast-tracking vaccine protocols much
as U.S. regulators accelerated the usually ponderous drug-approval process
to get AIDS drugs to market. With $100 million from the Bill and Melinda
Gates Foundation, the group doubled global spending on AIDS vaccine research
to $350 million and launched efforts to develop four "innovative vaccine
candidates" expressly for Africa.

Different strains of HIV predominate in different parts of the world, and
though it may turn out that a vaccine developed using one type would be
effective against other strains, scientists acknowledge the political
implications of research that, until now, has focused on the U.S. strain.

"Let's focus on the developing world," Berkley said. "I'm not worried that
if a vaccine is developed for South Africa, it will not be adapted for the
U.S. and Europe. But I am worried that if it is developed for the U.S. and
Europe, it might not be adapted for Africa for 10 years."

Studies of the Nairobi prostitutes and AIDS began in the mid-1980s at a
clinic operated by the city council in the slum of Pumwani that treated
sexually transmitted diseases. In 1985, shortly after a blood test for HIV
was developed, doctors from the University of Nairobi and Canada's
University of Manitoba began screening prostitutes for HIV. The result,
which showed two-thirds were infected, stunned everyone.

"This was a time when it was generally held that women didn't get AIDS,"
said Plummer, the Canadian researcher coordinating the study. "It all looks
so obvious in retrospect."

The studies, heralded fundamental truths about HIV: the importance of
commercial sex workers in spreading the disease, how much more easily it is
spread when sexually transmitted diseases are present, and the role of male
circumcision. (In Africa, at least, uncircumcised men contract HIV more
readily.)

But nothing was more remarkable than the continued presence at the clinic,
week after week, of women such as Kokutona. After years of having sex with
five or 10 men a day, they were aging veterans in a trade that was proving
increasingly lethal.

By the early 1990s, Plummer's team had assembled a list of sex workers who
had tested negative for HIV for nearly a decade. The finding was so
unexpected it encountered stiff resistance. The scientific paper laying out
the discovery took three years to find a publisher.

"It was a controversial idea," said Plummer, now scientific director of
Canada's National Microbiology Laboratory, the equivalent of the U.S.
Centers for Disease Control and Prevention. "People wanted us to tell them
'why,' too."

Andrew McMichael had a suspicion. A researcher at Oxford University in
England, McMichael was a leader in investigating killer T-cells. Most AIDS
vaccine research focused on antibodies, the cells that had proven key to
almost every vaccine ever developed. But McMichael had observed how poorly
antibodies stood up to HIV. The virus could be knocked flat by killer
T-cells, however, provided there were enough of them in the system.

And the prostitutes appeared to have lots of them.

"These women had very high levels of killer T-cells specific to HIV,
indicating they had been exposed to HIV but they had not been infected,"
said Omu Anzala, a leading University of Nairobi researcher. "So, can
T-cells protect against infection?"

The operating theory that emerged was that immunity built up like a callus:
The prostitutes' first encounter with HIV provoked T-cell production
sufficient to beat it back. The next exposure provoked even more T-cells,
which heightened immunity again, then again, until the women proved
essentially "uninfectable." The theory was reinforced when several women
left prostitution, then returned to it after falling on hard times, and
ended up contracting HIV.

At Oxford, McMichael's team set about creating a vaccine that would provoke
anyone's body to produce T-cells in much the same way that the presence of
the real virus appeared to provoke their production in the sex workers. The
vaccine they patented last year copies 44 bits, or epitopes, of HIV, which
are injected into volunteers after their immune systems have been "primed"
by a prior injection.

"What we are saying is all of us should be able to respond the way these
women are responding," Anzala said.

It is a classic approach. Edward Jenner discovered the world's first vaccine
by observing that dairy maids who had had cow pox did not contract
smallpox -- the milder cow pox being similar enough to smallpox to prime the
body against it. The Nairobi prostitutes, like a handful of uninfected sex
workers in Gambia and promiscuous gay men who have resisted infection,
constitute "the dairy maids of AIDS, and they have been ignored for years,"
said Jon Cohen, a science journalist and author of "Shots in the Dark: The
Wayward Search for an AIDS Vaccine."

Studies of blood taken from the 18 Kenyans who were injected with the
vaccine show "an 80 to 90 percent indication that it actually presents an
immune response," said McMichael. "I think the chances are better than
even -- probably a lot better than even -- that this is going to be
something useful."

By "useful," McMichael explained, he means the vaccine will make it more
difficult to become infected rather than provide absolute insurance against
the virus. But researchers will not know until final clinical trials are
well along, years from now.

Anzala, who lost a brother to AIDS, said it can't come soon enough for a
population wearying of the only form of prevention the world has offered for
20 years.

"We are reaching a level of fatigue," Anzala said. "People are told:
'Abstain. Use condoms.' People are saying: 'How long?' "



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