Biology Reference
In-Depth Information
multi-centered AIDS cohort study, early ADCC responses in patients
were associated with higher numbers of CD4
+
T-cells and the absence
of lymphadenopathy during the first two years of follow up.
28
In two
other studies, ADCC responses correlated inversely with plasma viral
load and also with CD4
+
T-cell counts.
24,29
The presence of neutral-
izing and ADCC activity in children born to HIV-infected mothers
correlated better with the clinical outcome.
30
Finally, it has been
shown that ADCC antibodies were present in cervicovaginal fluids in
HIV-1 infected women,
31
supporting the hypothesis that this form of
immunity can contribute in protection against HIV-1 at the site of
virus entry. In a recent study, Gomez-Roman
et al
. have shown that
priming with replicating adenovirus type 5 host range mutant-SIV
recombinants, followed by boosting with SIV gp120, elicited potent
ADCC activity that correlated with protection against the mucosal
challenge infection with pathogenic SIVmac251 in rhesus macaques.
32
This is the first study that demonstrates a good correlation between
the
in vitro
ADCC activity and
in vivo
reduced viremia; however, fur-
ther studies will be needed to establish the relationship between the
induction of ADCC and protection against HIV. The identification of
“ADCC epitopes” may help in designing strategies on means to pres-
ent and enhance the potency of these epitopes to prevent or control
the viral infection.
Neutralizing Epitopes Relevant for Vaccine
Development
As mentioned above, Env is the most important target for induction
of antibody responses against HIV. In addition, it has several known
CTL and helper T-cell epitopes that may provide targets for an effec-
tive anti-HIV vaccine. The
env
gene is expressed during the late phase
of viral transcription as the gp160 precursor protein. Translation of
the precursor protein is dependent on the viral Rev protein, which
binds to the rev responsive element (RRE) in Env mRNA and medi-
ates its nuclear export.
33
During the maturation of the virus, the
gp160 is proteolytically processed by cellular serine proteases to yield:
i) membrane-spanning domain termed gp41 and ii) an extracellular
