Å®ÉúСÊÓƵ

Å®ÉúСÊÓƵs seeking a vaccine for HIV should pay more attention to the
immune systems of people who have been repeatedly exposed to HIV without
apparently becoming infected. These immunological ‘successes’ could provide
important clues to the kind of immune response that protects against the
virus, say two researchers at the National Cancer Institute in Bethesda,
Maryland. So far, most studies have concentrated on people who have become
infected.

Gene Shearer and Mario Clerici, from the institute’s Experimental Immunology
Branch, have begun small-scale studies of uninfected men whose sexual behaviour
appears to put them at very high risk of infection. The studies are at an
early stage and other researchers have raised important questions about
their methods, but agree that the idea is worth pursuing.

Shearer, Clerici and their colleagues studied 5 gay men who had regularly
had anal intercourse with an infected partner, comparing them with a group
of 11 HIV-positive men and more than 100 so-called ‘low-risk’ uninfected,
heterosexual men of the same age. They found that the five men’s defence
cells ‘recognised’ proteins from HIV , even though it was impossible to
find antibodies to the virus or any other signs of infection. According
to the researchers, this suggests that an immune response to HIV can be
detected in people who have no antibodies to the virus (Journal of Infectious
Diseases, vol 165, p 1012).

The researchers took samples of blood from all the men. In the laboratory,
they stimulated T cells and mononuclear cells (white blood cells), with
synthetic proteins from HIV’s envelope protein. Mononuclear cells from all
five men produced a messenger protein, interleukin-2, suggesting that the
cells ‘recognised’ the viral proteins. Three out of five of the men also
had T cells that produced interleukin-2.

Ten months after the study began, one of the five men seroconverted
– that is, he produced antibodies to the virus, showing that he had become
infected. It is impossible to say whether he had been infected all along
despite negative tests, or whether he had been exposed to a new infection
during the study, says Shearer.

Do the results from the other four men imply that some people are protected
by their T cells against repeated infections with the virus? Not yet, for
important reasons. First, other scientists have reported finding ‘spurious’
T cells that respond to HIV in people who could not have been exposed to
infection. Jaap Goudsmit, at the Human Retrovirus Laboratory in the University
of Amsterdam, says this puts the study in question.

Shearer says, however, that the team found only 10 out of 155 men in
the ‘low-risk’ controls whose cells recognised HIV. This is a much lower
proportion than in the high-risk men and others at ‘moderate’ risk who were
also tested. He says it will be essential to study larger numbers of people,
and says this is already beginning.

Another question over the study, which the authors themselves raise,
is that the presence of T cells that recognise the virus may simply be a
forerunner of the antibodies that prove infection. The four uninfected men
may yet produce antibodies, but once again, it will not be easy to tell
when they became infected.

Shearer suggests that the men may have been exposed to very low levels
of virus in their previous sexual contacts. This may have stimulated an
immune response, but not led to seroconversion. ‘Our bottom line is that
AIDS researchers may have been looking for the immunologic failures and
ignoring what could turn out to be successes.’

The search for AIDS drugs could be boosted by the discovery of the crystal
structure of the HIV’s vital enzyme, reverse transcriptase. Lori Kohlstaedt
and her colleagues at the Howard Hughes Medical Institute in Connecticut
have built a detailed picture of the enzyme, which is the target of all
the current HIV drugs because HIV cannot replicate without it (Science,
vol 265, p 1783).