Biology Reference
In-Depth Information
eight animals were orally exposed to the pathogenic SHIV and four
of them were given post-exposure prophylaxis with three anti-HIV
mAbs (2F5, 2G12, and 4E10) at 40 mg/kg dose. All the animals that
received mAb therapy were protected from infection (p
0.028) and
their plasma, peripheral blood mononuclear cells, and lymph nodes
remained free of virus for more than a year. In contrast, all the con-
trols experienced high viral RNA levels and the loss of CD4
+
T-cells
and died (median survival time 5.5 weeks).
=
Challenges in Inducing Antibodies of Approriate
Specificity with Broadly Neutralizing Activity
During the course of natural infection, HIV triggers antibodies, cyto-
toxic T-cell (CTL), and CD4
+
T-helper immune responses. In gen-
eral, the primary peak of viremia declines before the appearance of
neutralizing antibodies against HIV Env. HIV-infected individuals
may generate potent neutralizing antibody responses to autologous
isolates, but these responses are slow to develop and take a long time
to mature.
3,82,111-116
Interestingly, some long-term non-progressors
who remained disease free for more than 10 years after HIV infection
developed strong, broadly cross-reactive neutralizing antibody
responses, which may have contributed toward their ability to control
infection.
117-120
The induction of antibody responses by monomeric
Env-based protein subunit vaccines is initially modest and requires
multiple boosts to induce strong responses. In addition, these antibod-
ies primarily recognized linear epitopes in the variable domains and
neutralized T-cell line-adapted (TCLA) virus isolates at significant dilu-
tions,
121,122
and fail to neutralize primary HIV-1 isolates.
3
Furthermore,
these non-conformational anti-gp120 specific antibodies are predom-
inantly subtype-specific and, to some extent, isolate-specific. However,
contrary to the earlier neutralization data, a recently published study
indicated that using a modified neutralization assay with an extended
incubation phase, these first generation of monomeric gp120 vaccines
can induce antibodies capable of neutralizing primary isolates.
123
Thus
for the fair comparisons of potential vaccine candidates there is an urgent
need to develop standardized neutralization assays.
