Potent anti-viral activity of a trispecific HIV neutralizing antibody in SHIV-infected monkeys.
Animals
Antiviral Agents
/ therapeutic use
Broadly Neutralizing Antibodies
/ immunology
CD8-Positive T-Lymphocytes
/ immunology
Cell Line, Tumor
HIV Antibodies
/ immunology
HIV-1
/ immunology
Humans
Immune Evasion
/ immunology
Immunotherapy
/ methods
Macaca mulatta
Simian Acquired Immunodeficiency Syndrome
/ therapy
Simian Immunodeficiency Virus
/ immunology
THP-1 Cells
Viremia
/ prevention & control
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
04 01 2022
04 01 2022
Historique:
received:
21
07
2021
revised:
20
10
2021
accepted:
10
12
2021
entrez:
5
1
2022
pubmed:
6
1
2022
medline:
17
2
2022
Statut:
ppublish
Résumé
Broadly neutralizing antibodies (bNAbs) represent an alternative to drug therapy for the treatment of HIV-1 infection. Immunotherapy with single bNAbs often leads to emergence of escape variants, suggesting a potential benefit of combination bNAb therapy. Here, a trispecific bNAb reduces viremia 100- to 1000-fold in viremic SHIV-infected macaques. After treatment discontinuation, viremia rebounds transiently and returns to low levels, through CD8-mediated immune control. These viruses remain sensitive to the trispecific antibody, despite loss of sensitivity to one of the parental bNAbs. Similarly, the trispecific bNAb suppresses the emergence of resistance in viruses derived from HIV-1-infected subjects, in contrast to parental bNAbs. Trispecific HIV-1 neutralizing antibodies, therefore, mediate potent antiviral activity in vivo and may minimize the potential for immune escape.
Identifiants
pubmed: 34986348
pii: S2211-1247(21)01703-4
doi: 10.1016/j.celrep.2021.110199
pmc: PMC8767641
mid: NIHMS1768962
pii:
doi:
Substances chimiques
Antiviral Agents
0
Broadly Neutralizing Antibodies
0
HIV Antibodies
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
110199Subventions
Organisme : NIAID NIH HHS
ID : U24 AI126683
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 AI999999
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI160607
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI131251
Pays : United States
Organisme : NIH HHS
ID : P40 OD028116
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI165080
Pays : United States
Informations de copyright
Copyright © 2021. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests L.X., Z.-y.Y., G.J.N., R.R.W., E.R., J.R.M., R.A.K., N.A.D.-R., T.Z., and A.P. are inventors on patent application WO 2017/074878, submitted by Sanofi, the United States of America, as represented by the Secretary, Department of Health and Human Services, and the National Institutes of Health, which discloses the use of anti-HIV antibodies. The other authors declare no competing interests.
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