A Bacterial Lipooligosaccharide that Naturally Mimics the Epitope of the HIV-Neutralizing Antibody 2G12 as a Template for Vaccine Design

摘要

The broadly neutralizing antibody 2G12 binds a fairly\udconserved cluster of oligomannose sugars on the\udHIV surface glycoprotein gp120, which has led to\udthe hypothesis that these sugars pose potential\udvaccine targets. Here, we present the chemical\udanalysis, antigenicity, and immunogenicity of a\udbacterial lipooligosaccharide (LOS) comprised of a\udmanno-oligosaccharide sequence analogous to the\ud2G12 epitope. Antigenic similarity of the LOS to oligomannose\udwas evidenced by 2G12 binding to the\udLOS and the inability of sera elicited against synthetic\udoligomannosides, but incapable of binding natural\udoligomannose, to bind the LOS. Immunization with\udheat-killed bacteria yielded epitope-specific serum\udantibodies with the capacity to bind soluble gp120.\udAlthough these sera did not exhibit specific anti-\udHIV activity, our data suggest that this LOS may\udfind utility as a template for the design of glycoconjugates\udto target HIV.