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NATURAL IMMUNITY TO HIV


OXFORD- The discovery of a small group of Gambian women with an apparent immunity to HIV infection could have large implications for the development of an AIDS vaccine.

A group of researchers from England, Gambia and Japan collaborated in the study of 20 female prostitutes in The Gambia, West Africa, who were persistently free of signs of HIV infection in spite of being exposed to the virus at least once per week for as long as five years. The women rarely utilized condoms with clients and had a high incidence of other sexually transmitted diseases. Thirty-five percent of prostitutes in the Gambia are HIV positive.

Immunological studies of the sera of the prostitutes showed that the women were generating highly specific cytotoxic T-lymphocyte (CTL) responses to both HIV-1 and HIV-2 peptides. The researchers were able to exclude the possibility that the women had been exposed but had not yet developed antibodies to HIV by using both culture and PCR repeatedly over three month period.

The researchers had to resort to some fancy laboratory work to detect the CTLs in the Gambian women. In HIV-infected individuals, HIV specific CTLs can be detected by using the patients own virus to stimulate CTLs in vitro. This would not work in uninfected people. One approach would have been to use exogenous samples of HIV to stimulate the CTLs in culture, but this did not work, possibly because of damage to CD4 cells needed to initiate the response. Ultimately, the HIV-specific CTLs were detected utilizing peptide epitopes which are bound in MHC (major histocompatability complex) molecules on the surface of infected cells and presented tot the T-cell receptors of the CTL.

"The most probable explanation for the finding of HIV-specific CTL, able to kill virus-infected cells, in apparently uninfected but repeatedly HIV-exposed women is that they have been immunized by exposure to HIV," notes Dr. Sarah Rowland-Jones of the Molecular Immunology Group at Radcliffe Hospital in Oxford.

These findings suggest that cytotoxic T-cell generation may be the most important element in creating protective immunity against HIV. The observation of a naturally occurring protective immunity to HIV provides a new rational for vaccine development. This study emphasizes the importance of utilizing cytotoxic T-lymphocyte induction in the design of AIDS vaccines, she stressed.

The most recent findings echo earlier reports of a group of comparable women in Nairobi who were uninfected in spite of constant HIV exposure. There have also been numerous reports of HIV-free babies born of infected mothers. Also, researchers reported on a sub-group of US men known to be exposed to HIV how had shown no signs or symptoms of disease for as long as 15 years.

A typical patient who is exposed to HIV goes through an acute viremic stage, followed by a phase of potent immune response during which the patient may do well for many years, until the immune system gives way, the viremia predominates and the patient progresses to AIDS.

Non-progressors, in contrast, do not suffer an acute phase and retain CD4 cell counts above 500. So far, none of the US sub-group, who have been followed for as long as 15 years, has become symptomatic.

"These rare patients provide a ray of hope to researchers and infected patients that it is possible to co-exist with HIV," said David Ho, M.D., Aaron Diamond AIDS Research Center, N.Y., who reported on the non-progressors at the Tenth International Conference on AIDS in Yokohama.

The data on the Gambian women were reported by Rowland-Jones et al., in Nature Medicine, v.1., n.1., 1/95.


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