Search for Aids cure shifts to prostitutes with immunity

• Women from Nairobi slum have antibodies capable of stopping virus before it attacks

Puzzled by a group of prostitutes who had resisted HIV infection even after being exposed to it, a group of scientists decided to study the unique women from Majengo slum in Nairobi.

From 1987, the researchers studied the women for over five years to find out what made them safe from the disease.

By 1992, they concluded that the women’s immune system could produce cells known as cytotoxic T-lymphocyte (CTL), also called killer T-cells that could destroy cells infected with HIV before the virus could multiply in the body.

Buoyed by these findings, donors in 1996 gave the researchers funds to establish conclusively why these women resisted HIV infection. However, it was not until 2000 that the women were found to generate killer-T cells, which disabled the virus before it could infect new cells.

Suffered setback

With this knowledge, the scientists rushed to the laboratories to develop a vaccine that could produce similar responses. They suffered a setback when 11 of the prostitutes became HIV positive.

Further investigations indicated that the women had stopped prostitution for about six months and only got infected after going back to the trade.

“A break from sex work was associated with a loss of HIV-specific CD8+ responses,” said the scientists in their 2000 report titled “Late seroconversion in HIV-resistant Nairobi prostitutes despite pre-existing HIV-specific CD8+ responses”.

According to the study, the prostitutes were only able to produce the killer T-cells after continually being exposed to HIV.

Under attack

“Their bodies felt they were constantly under attack as the women slept with between three and six men every day, some of whom were infected with HIV,” says Prof Omu Anzala, the director of Kenya Aids Vaccine Initiative.

When the women quit prostitution, their immune systems assumed all was well and reduced the production of the killer T-cells. By the time they went back to it, their bodies could not mount another defence immediately to counter HIV. They got infected.

The development raised fundamental questions on whether the vaccine based on the research was going to work, and if it did, how many times a person had to be vaccinated before he could be considered to be safe from the disease.

This meant that if the vaccine worked, an individual was going to be vaccinated on a regular basis to keep the immune system active. Such an approach, however, had drawbacks as it would not only be expensive, but would also have health implications, especially when one has to receive several vaccines over a short period.

The project was eventually shelved in 2006 after the vaccine failed to produce the killer T-cells in sufficient amounts that could convince scientists of its possible efficacy.

A few years later, another vaccine based on the same cellular immune response concept was tried in South Africa in what has come to be popularly known as the STEP Trial. This too failed.

Then came the Merck vaccine, which failed after entering the most advanced stage of the clinical trials.

But as these trials aborted, the active prostitutes in Majengo and other parts of Nairobi had little to worry about as they continued to resist the virus, confounding the scientists even further.

“We went back to basic science to understand why these women continued to have an excellent immune system,” says Dr Joshua Kimani, the clinical director of research for University of Nairobi and University of Manitoba.

Despite the drawbacks they have faced over the years, the researchers did not give up on the Majengo women.

Now, millions of shillings are being spent on fresh research to follow the Majengo prostitutes to establish their intriguing ability to defy HIV.

Scientists have renewed the efforts to understand why these women are a special breed. Many of the researchers, including Dr Kimani, still believe the solution to getting an effective vaccine lies with these women.

This quest for answers has seen researchers from University of Nairobi and University of Manitoba open up new centres in Korogocho and Kangemi to study more prostitutes there. The research will go on until 2010 and is expected to shed more light on resistance to HIV infection.

The women being recruited now are HIV negative prostitutes, who will then be studied for a period of three years to monitor their responses to HIV or any other sexually transmitted disease. So far, five per cent of them have been found to have the ability to resist HIV.

In recent times, some of the prostitutes have also been found to produce neutralising antibodies that stop HIV from infecting their cells. Unlike the killer T-cells, which kill an infected cell, the neutralising antibodies stop HIV from infecting the cell in first place.

Focus is now being put on finding neutralising antibodies in HIV positive individuals and then use them to develop an effective Aids vaccine. And the scientists appear to be succeeding on this front.

“What we are experiencing now is phenomenal and provides critical information of how we move forward and the massive work we need to undertake in this direction,” says Dr Wayne Koff of International Aids Vaccine Initiative.

In an interview with the Daily Nation, Dr Koff said his group had identified four antibodies that could neutralise the virus.
Immune systems

In this quest, the researchers are also paying attention to immune systems of individuals who have lived with HIV for the past three years without using anti-retroviral medicine. Some of them are believed to possess the neutralising antibodies.

Also to be studied are discordant couples — where one partner is HIV negative and the other positive.

Scientists are yet to decipher why one partner is able to remain negative for close to 10 years despite having unprotected sex with a HIV-positive spouse. They believe that unlocking this mystery could help them solve the HIV puzzle.