Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity
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| Authors: | Pantophlet, R; Trattnig, N; Murrell, S; Lu, NM; Chau, D; Rempel, C; Wilson, IA; Kosma, P |
| Year: | 2017 |
| Journal: | Nature Communications 8 Article Link (DOI) |
| Title: | Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity |
| Abstract: | Oligomannose-type glycans are among the major targets on the gp120 component of the HIV envelope protein (Env) for broadly neutralizing antibodies (bnAbs). However, attempts to elicit oligomannose-specific nAbs by immunizing with natural or synthetic oligomannose have so far not been successful, possibly due to B cell tolerance checkpoints. Here we design and synthesize oligomannose mimetics, based on the unique chemical structure of a recently identified bacterial lipooligosaccharide, to appear foreign to the immune system. One of these mimetics is bound avidly by members of a family of oligomannose-specific bnAbs and their putative common germline precursor when presented as a glycoconjugate. The crystal structure of one of the mimetics bound to a member of this bnAb family confirms the antigenic resemblance. Lastly, immunization of human-antibody transgenic animals with a lead mimetic evokes nAbs with specificities approaching those of existing bnAbs. These results provide evidence for utilizing antigenic mimicry to elicit oligomannose-specific bnAbs to HIV-1. |
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