Improved killing of HIV-infected cells using three neutralizing and non-neutralizing antibodies.
Adult
Antibodies, Monoclonal
/ administration & dosage
Antibodies, Neutralizing
/ administration & dosage
Antibody-Dependent Cell Cytotoxicity
/ immunology
Broadly Neutralizing Antibodies
/ administration & dosage
CD4-Positive T-Lymphocytes
/ immunology
Disease Reservoirs
/ virology
Female
HIV Antibodies
/ administration & dosage
HIV Infections
/ immunology
HIV-1
/ immunology
Humans
Immunotherapy
/ methods
In Vitro Techniques
Killer Cells, Natural
/ immunology
Kinetics
Male
Middle Aged
Neutralization Tests
Virus Latency
/ immunology
AIDS/HIV
Immunoglobulins
Immunotherapy
NK cells
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
09
12
2019
accepted:
24
06
2020
pubmed:
26
6
2020
medline:
26
2
2021
entrez:
26
6
2020
Statut:
ppublish
Résumé
The correlation of HIV-specific antibody-dependent cellular cytotoxicity (ADCC) responses with protection from and delayed progression of HIV-1 infection provides a rationale to leverage ADCC-mediating antibodies for treatment purposes. We evaluated ADCC mediated by different combinations of 2 to 6 neutralizing and non-neutralizing anti-HIV-1 Envelope (Env) mAbs, using concentrations ≤ 1 μg/mL, to identify combinations effective at targeting latent reservoir HIV-1 viruses from 10 individuals. We found that within 2 hours, combinations of 3 mAbs mediated more than 30% killing of HIV-infected primary CD4+ T cells in the presence of autologous NK cells, with the combination of A32 (C1C2), DH511.2K3 (MPER), and PGT121 (V3) mAbs being the most effective. Increasing the incubation of target and effector cells in the presence of mAb combinations from 2 to 24 hours resulted in increased specific killing of infected cells, even with neutralization-resistant viruses. The same combination eliminated reactivated latently HIV-1-infected cells in an ex vivo quantitative viral outgrowth assay. Therefore, administration of a combination of 3 mAbs should be considered in planning in vivo studies seeking to eliminate persistently HIV-1-infected cells.
Identifiants
pubmed: 32584790
pii: 135557
doi: 10.1172/JCI135557
pmc: PMC7524508
doi:
pii:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Broadly Neutralizing Antibodies
0
HIV Antibodies
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
Pagination
5157-5170Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI126619
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI120756
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI064518
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201000045C
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201700061C
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007392
Pays : United States
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