Induction of Transient Virus Replication Facilitates Antigen-Independent Isolation of SIV-Specific Monoclonal Antibodies.
CD8b depletion
SIV
antiretroviral therapy interruption
monoclonal antibodies
rhesus macaques
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
13 Mar 2020
13 Mar 2020
Historique:
received:
05
12
2019
accepted:
26
01
2020
entrez:
22
2
2020
pubmed:
23
2
2020
medline:
23
2
2020
Statut:
epublish
Résumé
Structural characterization of the HIV-1 Envelope (Env) glycoprotein has facilitated the development of Env probes to isolate HIV-specific monoclonal antibodies (mAbs). However, preclinical studies have largely evaluated these virus-specific mAbs against chimeric viruses, which do not naturally infect non-human primates, in contrast to the unconstrained simian immunodeficiency virus (SIV)mac239 clone. Given the paucity of native-like reagents for the isolation of SIV-specific B cells, we examined a method to isolate SIVmac239-specific mAbs without using Env probes. We first activated virus-specific B cells by inducing viral replication after the infusion of a CD8β-depleting mAb or withdrawal of antiretroviral therapy in SIVmac239-infected rhesus macaques. Following the rise in viremia, we observed 2- to 4-fold increases in the number of SIVmac239 Env-reactive plasmablasts in circulation. We then sorted these activated B cells and obtained 206 paired Ab sequences. After expressing 122 mAbs, we identified 14 Env-specific mAbs. While these Env-specific mAbs bound to both the SIVmac239 SOSIP.664 trimer and to infected primary rhesus CD4
Identifiants
pubmed: 32083148
doi: 10.1016/j.omtm.2020.01.010
pii: S2329-0501(20)30021-8
pmc: PMC7021589
doi:
Types de publication
Journal Article
Langues
eng
Pagination
225-237Subventions
Organisme : NIAID NIH HHS
ID : R01 AI108421
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI052056
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI052056
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI049120
Pays : United States
Organisme : NIH HHS
ID : R24 OD011161
Pays : United States
Organisme : NIH HHS
ID : K01 OD023032
Pays : United States
Organisme : NCRR NIH HHS
ID : R24 RR015371
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI073961
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NIAID NIH HHS
ID : F30 AI147881
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI094420
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NIH HHS
ID : P51 OD011106
Pays : United States
Informations de copyright
© 2020 The Author(s).
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