The author has summarized the history of discovery, the mechanism
and the
clinical significance of antibody-dependent
enhancement (ADE) of HIV infection. ADE has two major forms: (a)
complement-mediated antibody-dependent
enhancement (C-ADE) and (b) complement-independent Fc receptor-dependent
ADE (FcR-ADE). The most important
epitope responsible for the development of C-ADE-mediating antibodies is
present in the immunodominant region of
gp41 while antibodies mediating FcR-ADE react mainly with V3 loop of gp120.
There are at least three fundamentally
different hypotheses for the explanation of ADE in vitro:
(a) increased adhesion of HIV-antibody-(complement) complexes
to FcR or complement receptor carrying cells; (b) facilitation
of
HIV-target cell fusion by complement fragment deposited
on the HIV-virions and (c) complement activation products may
have
a non-specific stimulatory effect on target cells
resulting in enhanced virus production. FcR-ADE and C-ADE have been measured
in vitro mostly by using FcR-carrying
and complement receptor-carrying cell lines, respectively; no efforts have
been made to standardize these methods. Several
data support the possible clinical significance of FcR-ADE and C-ADE:
(a) Cross-sectional and longitudinal studies
indicate a correlation between the amounts of FcR-ADE and C-ADE-mediating
antibodies and clinical, immunological
and virological progression of the HIV-disease; (b) ADE may
facilitate maternal–infant HIV-1 transmission; (c) According
to experiments in animal models, ADE are present and may modify the course
of
SIV (simian immunodeficiency) infection
as well. The author raises a new hypothesis on the mechanism of the
in vivo effect of C-ADE. According to the hypothesis,
C-ADE-mediating antibodies exert their effect through enhancement of
HIV propagation and consequent facilitation of
the progression of HIV disease. Finally, according to observations from
animal experiments and human clinical trials it
cannot be excluded that ADE-mediating antibodies may develop, diminish
the
beneficial effect or may be harmful in
volunteers vaccinated with HIV-1 candidate vaccines.