Biology Reference
In-Depth Information
(Fig. 1B) and would thereby reduce the severity of the disease.
However, Mascola and colleagues have shown that the induction of
cellular responses using DNA vaccines in conjunction with passive
transfer of neutralizing antibodies did not offer additional protection
compared to the protection afforded by passive transfer of neutraliz-
ing antibodies alone.
8
Further studies will be needed to demonstrate
the advantage of inducing potent cellular and humoral responses by
an effective HIV vaccine for inducing the sterilizing immunity or
effectively controling the level of viral replication.
For the induction of neutralizing antibody responses, HIV Env
glycoprotein is the major antigenic target. However it has proven dif-
ficult to induce neutralizing antibody responses of appropriate speci-
ficity against diverse primary HIV-1 strains utilizing monomeric HIV
Env (i.e. gp120) glycoprotein. Therefore, a major challenge is to
develop novel strategies to identify and expose critical epitopes that
may be the target for inducing such broadly cross-reactive neutral-
izing antibodies with protective efficacy. This focus of this review is:
a) to capture the progress made in structural analysis of critical neutral-
izing antibodies, and b) to present strategies to design more potent
immunogens that may induce neutralizing antibodies of protective
efficacy.
Role of Antibodies in Protection Against HIV
Antibodies serve as a correlate of protection against some of the bac-
terial
9,10
and viral pathogens,
11
therefore targeting humoral responses
has been critical for developing prophylactic vaccines against these
targets. In the case of HIV, it has been a daunting task to make an
effective vaccine due to a lack of correlates of protection. During the
natural course of HIV infection or immunization with purified pro-
tein, a very strong humoral response is induced. However, most of
these antibodies are binding antibodies, and only a fraction of these
antibodies have neutralizing properties. These antibodies are termed
as “neutralizing antibodies” (nAb) because they neutralize the infec-
tious virus, and therefore prevent its entry to the cells or reduce the
level of inoculum, thereby reducing the severity of the disease.
12
