Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 09 2022
06 09 2022
Historique:
received:
11
02
2022
accepted:
16
08
2022
entrez:
6
9
2022
pubmed:
7
9
2022
medline:
9
9
2022
Statut:
epublish
Résumé
SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated intravenous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model.
Identifiants
pubmed: 36068229
doi: 10.1038/s41467-022-32783-2
pii: 10.1038/s41467-022-32783-2
pmc: PMC9446601
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Polysaccharides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5236Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Organisme : NIAID NIH HHS
ID : R61 AI161818
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI073961
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201500003I
Pays : United States
Organisme : NIH HHS
ID : P51 OD011106
Pays : United States
Organisme : NCI NIH HHS
ID : 75N91019D00024
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI052056
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Informations de copyright
© 2022. The Author(s).
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