Fine-mapping the immunodominant antibody epitopes on consensus sequence-based HIV-1 envelope trimer vaccine candidates.
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
25 Nov 2022
25 Nov 2022
Historique:
received:
08
06
2022
accepted:
07
11
2022
entrez:
26
11
2022
pubmed:
27
11
2022
medline:
27
11
2022
Statut:
epublish
Résumé
The HIV-1 envelope glycoprotein (Env) trimer is the key target for vaccines aimed at inducing neutralizing antibodies (NAbs) against HIV-1. The clinical candidate immunogen ConM SOSIP.v7 is a stabilized native-like HIV-1 Env trimer based on an artificial consensus sequence of all HIV-1 isolates in group M. In preclinical studies ConM SOSIP.v7 trimers induced strong autologous NAb responses in non-human primates (NHPs). To fine-map these responses, we isolated monoclonal antibodies (mAbs) from six cynomolgus macaques that were immunized three times with ConM SOSIP.v7 protein and boosted twice with the closely related ConSOSL.UFO.664 immunogen. A total of 40 ConM and/or ConS-specific mAbs were isolated, of which 18 were retrieved after the three ConM SOSIP.v7 immunizations and 22 after the two immunizations with ConSOSL.UFO.664. 22 mAbs (55%) neutralized the ConM and/or ConS virus. Cross-neutralization of ConS virus by approximately one-third of the mAbs was seen prior to ConSOSL.UFO.664 immunization, albeit with modest potency. Neutralizing antibodies predominantly targeted the V1 and V2 regions of the immunogens, with an apparent extension towards the V3 region. Thus, the V1V2V3 region is immunodominant in the potent NAb response elicited by two consensus sequence native-like HIV-1 Env immunogens. Immunization with these soluble consensus Env proteins also elicited non-neutralizing mAbs targeting the trimer base. These results inform the use and improvement of consensus-based trimer immunogens in combinatorial vaccine strategies.
Identifiants
pubmed: 36433972
doi: 10.1038/s41541-022-00576-9
pii: 10.1038/s41541-022-00576-9
pmc: PMC9700725
doi:
Types de publication
Journal Article
Langues
eng
Pagination
152Subventions
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : OPP1132237
Organisme : Bill & Melinda Gates Foundation
ID : INV-002022
Pays : United States
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : INV-008352/OPP1153692
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : OPP1115782
Organisme : NIAID NIH HHS
ID : P01 AI110657
Pays : United States
Organisme : amfAR, The Foundation for AIDS Research (amfAR)
ID : 109514-61-RKVA
Organisme : amfAR, The Foundation for AIDS Research (amfAR)
ID : 110182-69-RKVA
Informations de copyright
© 2022. The Author(s).
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