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
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
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
"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.