Biology Reference
In-Depth Information
immunogen with optimal exposure of this epitope. Based on oligomeric
modeling studies it seems that the immunologically silent face of Env
is likely to face toward the target cell membrane, and thus it is con-
ceptually possible that 2G12 may neutralize the virus by preventing
the interaction of the virus with target cells.
As with most pathogens, HIV-1 induces a polyclonal antibody
response to a wide array of epitopes on different viral proteins. Studies
of polyclonal sera have helped to identify the specificities of antibodies
that are associated with protection. It has been shown that sera col-
lected from some HIV-infected individuals neutralize primary isolates
(using CCR5 as a co-receptor, R5).
82,83
In addition, several investigators
have generated potent neutralizing monoclonal antibodies from the
bone marrow of HIV
+
patients against critical functional and conserved
epitopes (Table 1), such as the ones in the CD4-binding site (CD4-
BS),
38
CD4-inducible epitopes (CD4-i),
46
carbohydrate-dependent epi-
tope,
79
and the epitopes present in variable loops
58,59,84-86
and gp41
regions of Env.
87-89
The relative position of these epitopes compared to
the host and target membrane and the complexity of the binding sites
is presented in Fig. 3. Furthermore, neutralizing antibodies from the
HIV
+
patient's sera can be affinity-purified on a gp120 column,
83,90
suggesting that neutralizing epitopes are present and exposed on gp120.
Induction of antibodies to each of these epitopes may ultimately be use-
ful in protecting individuals against HIV-1 infection; however, presen-
tation of each of these epitopes in context to a vaccine is the challenge.
During the past few years, considerable attention has been
focused on neutralizing antibodies; therefore, two major points need
to be addressed: (i) characterizing the fine specificity of protective
antibodies, and (ii) means to elicit these protective antibodies by
immunization.
Protective Efficacy of Neutralizing Monoclonal
Antibodies in Passive Transfer
It is generally accepted that antibodies are important for protection
against HIV infection; however, so far it has been difficult to induce
protective antibodies of the appropriate specificity by vaccination.
To have a better understanding of the role of neutralizing antibodies
