Biology Reference
In-Depth Information
However, only a proportion of all neutralizing antibodies have pro-
tective efficacy. Until recently, it was generally believed that not all
Env spikes need to be engaged by these nAbs for them to be efficient
in controlling or preventing viral replication. However, Yang and col-
leagues demonstrated that virus neutralization requires essentially all
of the functional trimers to be occupied by at least one antibody.
Their model applies to antibodies differing in neutralizing potency
and to virus isolates with different neutralization sensitivities.
13
However, recent data suggest that in addition to nAbs, there is
another class of antibodies that exert their protective efficacy by
inducing antibody dependent cellular cytotoxicity (ADCC); i.e. they
direct the killing of infected cells through recognition of viral proteins
on cell surfaces.
Possible Steps for Immune Intervention
There are several possible steps during the virus lifecycle (pre- and
post-attachment events) where immune intervention is possible and
may prevent the infection or control viral replication, as illustrated in
Fig 2. Since binding of HIV to its receptor (CD4) and co-receptor
(e.g. CCR5) is critical for viral entry in new CD4
+
T-cells, a logical
and attractive strategy could be to prevent the interaction of the HIV
virion with its cellular receptor or co-receptor. Other possible and
attractive strategies could be to target other important post-attach-
ment events such as: a) the formation of a coiled-coil structure lead-
ing to virus/host membrane fusion
14-17
; b) primary un-coating of the
virus in the cytoplasm; c) transcription or virus assembly; and d) bud-
ding of the new virion. For HIV-1, inhibition of receptor binding has
been seen for different types of antibodies, including: i) those that tar-
get carbohydrate of the virus glycoprotein
18,19
; ii) those that target dif-
ferent
adhesion molecules
; iii) those specific for various regions of
gp120 such as the
CD4 binding domain
, the
CD4-induced (CD4i)
epitope
(located in the bridging sheet of gp120 that is created or
exposed when gp120 interacts with CD4),
20
and the
variable loops
,
V2 and V3; iv) those that target the
co-receptor binding site
21
; and
(v) another class of mAbs such as 2F5, 4E10, or Z13 that may
