Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual.

Dissecting antibody specificities in the plasma of HIV-1 infected individuals that develop broadly neutralizing antibodies (bNAbs) is likely to provide useful information for refining target epitopes for vaccine design. Several studies have reported CD4-binding site (CD4bs) antibodies as neutralization determinants in the plasma of subtype B-infected individuals; however there is little information on the prevalence of CD4bs specificities in HIV-infected individuals in India. Here, we report on the presence of CD4bs antibodies and their contribution to virus neutralization in the plasma from a cohort of HIV-1 infected Indian individuals.

The presence of glutamine at position 315 but not epitope masking predominantly hinders HIV subtype C neutralization by the anti-V3 antibody B4e8.

Antibody B4e8 exhibits modest cross-neutralizing activity, with preference for HIV subtype B. This preference might be explained by B4e8׳s extensive interaction with Arg315, which occurs at the center of most subtype B V3 sequences but is replaced by Gln in subtype C. The extent to which B4e8׳s ability to neutralize subtype C strains is hindered by Gln315 and/or other factors, e.

A bacterial lipooligosaccharide that naturally mimics the epitope of the HIV-neutralizing antibody 2G12 as a template for vaccine design.

The broadly neutralizing antibody 2G12 binds a fairly conserved cluster of oligomannose sugars on the HIV surface glycoprotein gp120, which has led to the hypothesis that these sugars pose potential vaccine targets. Here, we present the chemical analysis, antigenicity, and immunogenicity of a bacterial lipooligosaccharide (LOS) comprised of a manno-oligosaccharide sequence analogous to the 2G12 epitope. Antigenic similarity of the LOS to oligomannose was evidenced by 2G12 binding to the LOS and the inability of sera elicited against synthetic oligomannosides, but incapable of binding natural oligomannose, to bind the LOS.

An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site.

A major priority in HIV vaccine research is the development of an immunogen to elicit broadly neutralizing antibodies (NAbs). Monoclonal antibody (mAb) b12 is one of now several broadly neutralizing mAbs that bind epitopes overlapping the CD4-binding site (CD4bs) on HIV-1 gp120 and that serve as templates to engineer effective immunogens. We are exploring a strategy whereby extra glycans are incorporated onto gp120 to occlude the epitopes of non-neutralizing mAbs while maintaining exposure of the b12 site.