Karl Vick
Washington Post Foreign Service

p. A01.

AIDS Vaccine Hopes Rise From Africa

'Killer T-Cells' Seem to Naturally Protect Some Prostitutes

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?'"

© 2001 The Washington Post Company