Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity
| Autor: | Ian A. Wilson, Dennis Chau, Ralph Pantophlet, Caitlin Rempel, Sasha Murrell, Paul Kosma, Nino Trattnig, Naiomi Lu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Glycan Protein Conformation Glycoconjugate Science Oligosaccharides General Physics and Astronomy HIV Infections CHO Cells HIV Antibodies HIV Envelope Protein gp120 medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Cricetulus 0302 clinical medicine Immune system Antigen medicine Animals Humans lcsh:Science Mammals chemistry.chemical_classification Infectivity Multidisciplinary Bacteria biology Molecular Mimicry virus diseases General Chemistry HIV envelope protein Antibodies Neutralizing Virology 3. Good health Molecular mimicry HEK293 Cells 030104 developmental biology Carbohydrate Sequence chemistry HIV-1 biology.protein lcsh:Q Rats Transgenic Antibody 030215 immunology |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-12 (2017) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-017-01640-y |
| Popis: | 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. Neutralizing antibodies to oligomannose glycans on HIV Env are difficult to elicit, possibly due to B cell tolerance. Here, Pantophlet et al. synthesize mimetics based on a bacterial oligosaccharide and show that they evoke HIV-neutralizing antibody responses in animals with a human Ig repertoire. |
| Databáze: | OpenAIRE |
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