Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
07 10 2019
07 10 2019
Historique:
received:
25
01
2019
revised:
29
04
2019
accepted:
25
06
2019
pubmed:
28
7
2019
medline:
11
6
2020
entrez:
27
7
2019
Statut:
ppublish
Résumé
Many tested vaccines fail to provide protection against disease despite the induction of antibodies that bind the pathogen of interest. In light of this, there is much interest in rationally designed subunit vaccines that direct the antibody response to protective epitopes. Here, we produced a panel of anti-idiotype antibodies able to specifically recognize the inferred germline version of the human immunodeficiency virus 1 (HIV-1) broadly neutralizing antibody b12 (iglb12). We determined the crystal structure of two anti-idiotypes in complex with iglb12 and used these anti-idiotypes to identify rare naive human B cells expressing B cell receptors with similarity to iglb12. Immunization with a multimerized version of this anti-idiotype induced the proliferation of transgenic murine B cells expressing the iglb12 heavy chain in vivo, despite the presence of deletion and anergy within this population. Together, our data indicate that anti-idiotypes are a valuable tool for the study and induction of potentially protective antibodies.
Identifiants
pubmed: 31345930
pii: jem.20190164
doi: 10.1084/jem.20190164
pmc: PMC6780997
doi:
Substances chimiques
Antibodies, Anti-Idiotypic
0
Antibodies, Neutralizing
0
HIV Antibodies
0
Banques de données
PDB
['2NY7', '6OL6', '6OL5']
GENBANK
['MK775682', 'MK775686', 'MK775683', 'MK775687', 'MK775684', 'MK775688', 'MK775685', 'MK775689']
Types de publication
Clinical Trial
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
2331-2347Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM095421
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI081625
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI127249
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI073148
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI138212
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI059714
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI122912
Pays : United States
Informations de copyright
© 2019 Bancroft et al.
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