Format

Send to

Choose Destination
Nat Commun. 2017 Nov 17;8(1):1601. doi: 10.1038/s41467-017-01640-y.

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

Author information

1
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada, V5A1S6. rpantophlet@sfu.ca.
2
Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, BC, Canada, V5A1S6. rpantophlet@sfu.ca.
3
SFU Interdisciplinary Research Centre for HIV, Simon Fraser University, Burnaby, BC, Canada, V5A1S6. rpantophlet@sfu.ca.
4
Department of Chemistry, University of Natural Resources and Life Sciences, A-1190, Vienna, Austria.
5
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
6
Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
7
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada, V5A1S6.
8
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA. wilson@scripps.edu.
9
Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA. wilson@scripps.edu.
10
IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA. wilson@scripps.edu.
11
Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, 92037, USA. wilson@scripps.edu.
12
Department of Chemistry, University of Natural Resources and Life Sciences, A-1190, Vienna, Austria. paul.kosma@boku.ac.at.

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.

PMID:
29150603
PMCID:
PMC5693931
DOI:
10.1038/s41467-017-01640-y
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center