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Natural
immunity to HIV?
In recent years, tantalizing reports have been circulating
regarding the possibility that some individuals who have been
exposed to HIV were only transiently infected with HIV. Understanding
the reasons why these people remain uninfected should shed
light on the nature of protective immunity against HIV.
All infected people exhibit immune responses against HIV.
One such response, production of antibodies against HIV, is
diagnostic of infection. The problem is, these immune responses
fail to provide protection against the virus, and people become
sick despite being sero-positive (that is, having antibodies
in their blood (serum) against HIV).
Some
researchers have studied sero-negative persons who have been
repeatedly exposed to HIV, because of the possibility that
such people had successfully managed to fend off infection
with an appropriate immune response. Had HIV established an
infection, antibodies against HIV would have been present
in their blood, yet the immune cells of some sero-negative
people respond to HIV in test tube experiments as though the
cells had encountered the virus before.
The
antibodies made against HIV that are detected in the standard
HIV test, belong to a class of proteins called immunoglobulin
G (IgG). Antibodies are also produced at mucosal surfaces
where transmission of HIV usually occurs, but unlike the IgG
species of antibody present in blood, mucosal antibodies belong
to a different class of protein called immunoglobulin A (IgA).
IgA against HIV would not be detected in an HIV test. Some
researchers believe that the immune responses most likely
to protect against transmission of HIV are those that occur
at mucosal surfaces. Could repeatedly exposed, yet uninfected,
people have IgA against HIV?
Recently, a group of researchers in Italy headed by Dr. Mario
Clerici examined a group of sero-positive individuals and
their sero-negative partners for IgA against HIV. As expected,
all sero-positive people had both IgG and IgA against HIV.
The sero-negative partners had no IgG of course. The key finding
is that these individuals expressed IgA antibodies against
HIV. Furthermore, when several of the sero-negative partners
were followed up one year following the cessation of "at-risk"
sex, they remained sero-negative and their IgA levels were
reduced.
One
obvious conclusion is that these individuals were protected
from HIV infection by virtue of high levels of IgA antibodies
at their mucosal linings. In this model, one might imagine
that those who remained sero-negative responded to HIV with
a sufficiently potent IgA response. Those who become infected
had an initially ineffectual or absent IgA response, and expressed
copious amounts of IgA later (because HIV infection is active
and chronic).
Remember
that the individuals in this study were pre-selected, so that
any genetic or biological attributes responsible for the protective
immunity had also been pre-selected. In other words, the odds
are very low that protective immunity would occur in any one
individual; the researchers had defined a cohort that selected
for the lucky minority.
However,
one cannot jump to conclusion regarding cause and effect.
It is possible that some other attribute or immune response
conferred protective immunity on these sero-negative individuals.
It is also possible that these individuals had been infected
and that if one followed them long enough they would eventually
exhibit signs of the infection (this possibility is less likely,
but still plausible).
If mechanisms that protect people from HIV infection can be
determined, this information might inform strategies for the
development of a preventative HIV vaccine, and for controlling
HIV in infected individuals.
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