biggest obstacle to an AIDS vaccine is the virus itself

By far the biggest obstacle to an AIDS vaccine is the virus itself. For one thing, HIV has many different strains, called subtypes, and the major one in the United States and Europe — and hence the one most used in most candidate vaccines — is different from the dominant subtypes in Africa. No one knows if a vaccine designed against one subtype will protect against infection by a different one.

Then too, people’s immune systems are different, composed of various “HLA types.” Even if infected with the same strain, people often display different viral epitopes on the surface of their cells. These differences tend to correspond with ethnicity, so a vaccine that protects most whites might not be as effective among Asians or Africans.

McMichael has tackled these problems by making his vaccine out of fragments of the HIV subtype most common in Kenya, subtype A. In addition, he has included enough epitopes to cover probably every HLA type in East Africa. Still, McMichael’s vaccine contains only 44 epitopes, plus a whole viral gene. Are these enough? And are killer T-cells truly the key to protection?

Most of the uninfected prostitutes appear to produce a special antibody in the place where HIV first enters them: the mucosal tissue of their vaginas. So, should a vaccine induce site-specific antibodies? There are other experimental vaccines that attempt to do exactly that.

No one knows the answers to these questions, but Africans are not waiting for the West to solve the problem. “I lost my own brother to AIDS two years ago,” says Anzala, who has dedicated many years to studying the Pumwani sex workers’ immune systems. “That really devastated me, because with all the knowledge I had. . . . ” His voice trails off; then he snaps back and adds, “We can’t wait for something to come from the U.S. No. We have to participate.”

Indeed, African scientists are actively contributing to the research, providing ideas and laboratory research, pushing scientists to put candidate vaccines into trials on their continent, and insisting that the world develop vaccines that are likely to work against their subtypes of HIV. Uganda is already hosting the continent’s first human trial of an AIDS vaccine, and Ugandan researchers are conducting the sophisticated laboratory analyses needed to evaluate the trial. South Africa — which accomplished the world’s first successful heart transplant — has the most developed biomedical research capacity in Africa. President Thabo Mbeki has declared an AIDS vaccine a top priority, committing government funds to a soup-to-nuts research effort. “We’re not just trial sites in Africa,” says Quarraisha Abdool-Karim, a veteran South African AIDS researcher. “We have an intellectual contribution to make.”

While the Africans are pushing as hard as they can, AIDS scientists around the world are also putting vaccines high on the agenda. The U.S. National Institutes of Health, which dwarfs any other medical research agency in the world, and which spends more than a billion dollars on AIDS research alone, used to give vaccine research less than 10 percent of its AIDS budget, less than any other category of HIV research. But over the last three years it has ratcheted up that percentage, and it has brought in Nobel laureate David Baltimore to lead its effort. Whereas the mood was once pessimistic, most scientists now believe a vaccine is possible.

But even if the scientific obstacles are overcome, another hurdle will remain.

Vast, impoverished, and riven by civil war, the Democratic Republic of the Congo is the hardest place on earth to conduct a vaccination campaign. But three times this year, thousands of health workers went out into the countryside, squirting the life-saving pink liquid into the mouths of millions of Congolese babies. In a village outside the town of Mbuji-Mayi, proud mothers held up their vaccinated babies as the whole village celebrated the immunizations. Despite war, the World Health Organization predicts that within a year, the Congo and the world may be polio-free. This is the dream of AIDS-vaccine workers.

But it is also the nightmare, because despite a cheap and effective vaccine, polio is being wiped out only now, about four decades after it was banished from America. Once an AIDS vaccine is developed, will Africa have to wait 40 years for it?

If the vaccine based on the Pumwani prostitutes works, Africa will get it soon. That’s because its development is sponsored by the International AIDS Vaccine Initiative (IAVI), which is laying the groundwork for something that has never happened before: simultaneous delivery of a vaccine to the developed and developing worlds.

IAVI president Seth Berkley, who worked in Uganda during the early days of the AIDS epidemic, is a man in perpetual motion. He has lobbied the World Bank, the EU, the G-7, and any other deep pocket that will listen to create a fund for distributing an AIDS vaccine in the developing world. In addition, IAVI is making sure the vaccines it bankrolls will be available in poor countries.

Berkley has convinced Bill Gates to give his organization $26.5 million and the British government another $23 million; IAVI invests these funds in promising vaccines, fast-tracking them through the pipeline. “We are like a venture-capital firm,” Berkley says. “But instead of demanding 50 percent of the profits, we want access for the poor.”

Essentially, IAVI negotiates agreements that give the manufacturer the option to make the vaccine affordable for developing countries. But if they don’t, says Berkley, “We retain a series of rights that allow us to get the vaccine out there.”

At the Pumwani clinic, Kimani, the young doctor, says, “We promised the women that anything that came out of the research will benefit them. And they are already asking about the vaccine.” In fact it will be years before the vaccine is ready for large-scale efficacy trials, let alone before researchers know whether it actually protects people. Even when pushed, science crawls.

Meanwhile, Kimani explains what happens as the women approach death. “When they are clearly deteriorating, we call them in. They ask, ‘Am I not doing well?’ And we say, ‘Maybe it’s time to go home to the village.’ ” Kimani pauses. “We have money we can give them to go home to their family.” That statement sinks in, and then Kimani says — shouts, almost — “We desperately need a vaccine!”

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