|Title||Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Pantophlet R, Trattnig N, Murrell S, Lu N, Chau D, Rempel C, Wilson IA, Kosma P|
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.
|Alternate Journal||Nat Commun|
|PubMed Central ID||PMC5693931|
|Grant List||UM1 AI100663 / AI / NIAID NIH HHS / United States |
P41 GM103311 / GM / NIGMS NIH HHS / United States
R01 AI084817 / AI / NIAID NIH HHS / United States
P41 GM103694 / GM / NIGMS NIH HHS / United States
R24 GM098791 / GM / NIGMS NIH HHS / United States
Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity.