Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity.

TitleBacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity.
Publication TypeJournal Article
Year of Publication2017
AuthorsPantophlet R, Trattnig N, Murrell S, Lu N, Chau D, Rempel C, Wilson IA, Kosma P
JournalNat Commun
Volume8
Issue1
Pagination1601
Date Published11/17/2017
ISSN2041-1723
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.

DOI10.1038/s41467-017-01640-y
Alternate JournalNat Commun
PubMed ID29150603
PubMed Central IDPMC5693931
Grant ListUM1 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
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