Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.
AIDS Vaccines
/ immunology
Animals
Antibodies, Neutralizing
/ immunology
Antibody Formation
Antigens, Viral
/ immunology
Epitopes
/ immunology
Female
Glycoproteins
/ immunology
HIV Antibodies
/ immunology
HIV Infections
/ virology
HIV-1
/ metabolism
Immunization
Polysaccharides
/ metabolism
Rabbits
env Gene Products, Human Immunodeficiency Virus
/ immunology
Env trimer
HIV-1
SOSIP
antibodies
epitope
glycan hole
immunization
neutralization
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
15 02 2019
15 02 2019
Historique:
received:
19
09
2018
accepted:
16
11
2018
pubmed:
30
11
2018
medline:
7
1
2020
entrez:
30
11
2018
Statut:
epublish
Résumé
In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals. The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces. For BG505 trimers, the dominant autologous NAb epitope in rabbits involves residues that line a cavity caused by the absence of a glycan at residue 241. Here, we blocked this epitope in BG505 SOSIPv4.1 trimer immunogens by knocking in an N-linked glycan at residue 241. We then opened holes elsewhere on the trimer by knocking out single N-linked glycans at residues 197, 234, 276, 332, and 355 and found that NAb responses induced by the 241-glycan-bearing BG505 trimers were frequently redirected to the newly opened sites. The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site. We also attempted to knock in the N289-glycan to block the sole autologous NAb epitope on the B41 SOSIP.v4.1 trimer. Although a retrospective analysis showed that the new N289-glycan site was substantially underoccupied, we found some evidence for redirection of the NAb response to a neoepitope when this site was knocked in and the N356-glycan site knocked out. In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.
Identifiants
pubmed: 30487280
pii: JVI.01656-18
doi: 10.1128/JVI.01656-18
pmc: PMC6363999
pii:
doi:
Substances chimiques
AIDS Vaccines
0
Antibodies, Neutralizing
0
Antigens, Viral
0
Epitopes
0
Glycoproteins
0
HIV Antibodies
0
Polysaccharides
0
env Gene Products, Human Immunodeficiency Virus
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
Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI036082
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI036082
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI131873
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI110657
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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