Wednesday, 19 November 2008 09:44

Renewed interest in prostitutes with unique immunity

Written by Arthur Okwemba

HIV/AIDSPuzzled by a section of prostitutes in Majengo slums who had managed to resist HIV infection even after being exposed to it, a group of scientists decided in 1987 to understand why this was the case.

This amazing finding made them follow these women keenly for over five years to find out what made them tick.

By 1992, they concluded that the women’s immune system was able to elicit certain cells known as cytotoxic T-lymphocyte (CTL), also called killer T-cells that had the ability to destroy the HIV infected cell before the virus replicated.

Buoyed by these findings, donors in 1996 gave the researchers funds to establish conclusively why these women were able to resist HIV infection.

But it was not until 2000 when the mechanism of resistance was fully established. The women were found to generate specific killer-T cells that were able to disable the virus before infecting new cells.

With this knowledge, the scientists rushed to the laboratories to develop a vaccine that could generate similar responses in other people who were HIV negative.

Meanwhile, 11 of the women who had successfully shown this ability to resist HIV became positive. Scientists were alarmed.

Further investigations indicated that these women had left the sex business for a minimum of six months and when they resumed, they got infected.

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

“Seroconversion generally occurs in the absence of detectable CTL escape mutations and may relate to the waning of HIV-specific CD8+ responses due to reduced antigenic exposure,” the report added.

This meant the women’s immune system was able to elicit the Killer T cells because of continually being exposed to the virus during sex intercourse.

“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 current Director of Kenya Aids Vaccine Initiative (KAVI).

But when they left the business, their immune system assumed all was well and reduced the production of CTL cells. And by the time they went back to commercial sex, their bodies could not mount another defense mechanism immediately to counter the HIV infection. They got infected.

The development raised fundamental questions on whether the vaccine was going to work, and if it did, the number of times a person had to be vaccinated.

This then meant that if it worked, an individual was going to be vaccinated on a regular basis to keep the immune system active. Such an approach, however, had drawbacks in terms of costs and health concerns, especially when one has to receive several jabs of vaccines in a short span of time. 

Unfortunately, in 2006, after five years of trials, this vaccine failed to elicit the CTL cells in amounts to convince scientists of its possible efficacy. It was shelved.

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 STEP Trial. It also failed.

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

But as these vaccines trials aborted and scientists went into shock, the prostitutes in Majengo and other parts of Nairobi were smiling. They continued to resist this virus in a more robust way than ever before, confounding the scientists.

“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 for University of Nairobi and University of Manitoba research activities.

While all this was happening, many Kenyans thought these failures had shut the door on research in areas like Majengo and the scientists had forgotten about these prostitutes. They were wrong.

Away from the public scrutiny and major upsets, the Majengo women have acquired new status and scientists are not letting them go.

In fact, hundreds of millions of shillings are now being pumped into research to follow the Majengo woman and other prostitutes to establish their intriguing ability to defy HIV infection even after being exposed to the virus.

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

This search for answers has seen researchers from University of Nairobi in collaboration with University of Manitoba open up new centres in Korogocho and Kagemi to study more prostitutes in these areas.

The new research runs up to 2010, and is expected to shed more light on mechanism of resistance to HIV infection.

The women being recruited now are HIV negative prostitutes, who will then be followed for a period of three years to monitor their acquisition of HIV or any other STDs. So far, 5 percent of them have been found to have the ability to resist HIV infection.

In recent times, some of these women have also been found to possess neutralizing antibodies that have the ability to stop the virus from infecting the cells. Unlike the CTL’s which kill an infected cell, the neutralizing antibodies stop HIV from infecting the cell in first place.

A lot of focus is now being placed on finding broadly neutralising antibodies in HIV positive individuals and then using this knowledge to develop an effective AIDS vaccine. The good news is, scientists are getting somewhere on this front.

In Africa, of the 1,700 HIV positive people who have been screened in the past one year, 170 have HIV neutralising antibodies. Some of these are said to be commercial sex workers.

“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 (IAVI).

In an interview with AWC, Wayne said they have managed to identify four antibodies with ability to neutralise the virus and are currently studying them to see which ones are broadly neutralising-those with ability to neutralise different types of HIV strains such as A, B, C and D.

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

Buoyed by these new findings, IAVI is going to set aside between 30 and 50 per cent of its budget on vaccine discovery on the identification and development of a vaccine with the ability to elicit broadly neutralising antibodies, according to Dr Koff.

In addition to these female prostitutes, the spotlight has also turned to discordant couples – where one partner is HIV negative and the other positive.

Scientists are yet to decipher why one partner is able to remain HIV negative for close to 10 years when having unprotected sex with the HIV positive one.

Many researchers in this area admit they are groping in the dark to lay their hands on just what is behind this resistance.

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