Development of a VRC01-class germline targeting immunogen derived from anti-idiotypic antibodies.
B cell receptor
HIV-1
anti-idiotypic antibodies
antibody heavy chain
antibody light chain
broadly neutralizing antibodies
vaccines
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
04 05 2021
04 05 2021
Historique:
received:
30
10
2020
revised:
08
03
2021
accepted:
13
04
2021
entrez:
5
5
2021
pubmed:
6
5
2021
medline:
11
2
2022
Statut:
ppublish
Résumé
An effective HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs). Broad and potent VRC01-class bNAbs have been isolated from multiple infected individuals, suggesting that they could be reproducibly elicited by vaccination. Several HIV-1 envelope-derived germline-targeting immunogens have been designed to engage naive VRC01-class precursor B cells. However, they also present off-target epitopes that could hinder development of VRC01-class bNAbs. We characterize a panel of anti-idiotypic monoclonal antibodies (ai-mAbs) raised against inferred-germline (iGL) VRC01-class antibodies. By leveraging binding, structural, and B cell sorting data, we engineered a bispecific molecule derived from two ai-mAbs; one specific for VRC01-class heavy chains and one specific for VRC01-class light chains. The bispecific molecule preferentially activates iGL-VRC01 B cells in vitro and induces specific antibody responses in a murine adoptive transfer model with a diverse polyclonal B cell repertoire. This molecule represents an alternative non-envelope-derived germline-targeting immunogen that can selectively activate VRC01-class precursors in vivo.
Identifiants
pubmed: 33951425
pii: S2211-1247(21)00417-4
doi: 10.1016/j.celrep.2021.109084
pmc: PMC8127986
mid: NIHMS1700552
pii:
doi:
Substances chimiques
AIDS Vaccines
0
HIV Antibodies
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
109084Subventions
Organisme : NIAID NIH HHS
ID : R01 AI081625
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI127249
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM133894
Pays : United States
Organisme : NIH HHS
ID : S10 OD021832
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI138212
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI122912
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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