The mechanistic basis of protection by non-neutralizing anti-alphavirus antibodies.
Alphavirus
/ immunology
Alphavirus Infections
/ immunology
Animals
Antibodies, Monoclonal
/ immunology
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Epitope Mapping
Female
HEK293 Cells
Humans
Male
Mice, Inbred C57BL
Monocytes
/ metabolism
Musculoskeletal Diseases
/ immunology
Myeloid Cells
/ metabolism
Receptors, IgG
/ metabolism
Recombinant Proteins
/ metabolism
Viral Proteins
/ chemistry
Virion
/ metabolism
Fc effector
alphavirus
antibody
epitope
mapping
monocytes
neutralization
pathogenesis
protection
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
06 04 2021
06 04 2021
Historique:
received:
28
10
2020
revised:
19
01
2021
accepted:
16
03
2021
entrez:
7
4
2021
pubmed:
8
4
2021
medline:
27
1
2022
Statut:
ppublish
Résumé
Although neutralizing monoclonal antibodies (mAbs) against epitopes within the alphavirus E2 protein can protect against infection, the functional significance of non-neutralizing mAbs is poorly understood. Here, we evaluate the activity of 13 non-neutralizing mAbs against Mayaro virus (MAYV), an emerging arthritogenic alphavirus. These mAbs bind to the MAYV virion and surface of infected cells but fail to neutralize infection in cell culture. Mapping studies identify six mAb binding groups that localize to discrete epitopes within or adjacent to the A domain of the E2 glycoprotein. Remarkably, passive transfer of non-neutralizing mAbs protects against MAYV infection and disease in mice, and their efficacy requires Fc effector functions. Monocytes mediate the protection of non-neutralizing mAbs in vivo, as Fcγ-receptor-expressing myeloid cells facilitate the binding, uptake, and clearance of MAYV without antibody-dependent enhancement of infection. Humoral protection against alphaviruses likely reflects contributions from non-neutralizing antibodies through Fc-dependent mechanisms that accelerate viral clearance.
Identifiants
pubmed: 33826892
pii: S2211-1247(21)00276-X
doi: 10.1016/j.celrep.2021.108962
pmc: PMC8055377
mid: NIHMS1691260
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Receptors, IgG
0
Recombinant Proteins
0
Viral Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
108962Subventions
Organisme : NIAID NIH HHS
ID : R01 AI123348
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142790
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI141436
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI114816
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201700060C
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and the Carnival Corporation and on the Scientific Advisory Board of Moderna and Immunome. The Diamond laboratory has received sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions.
Références
Am J Trop Med Hyg. 2019 Jun;100(6):1541-1544
pubmed: 31017081
Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27637-27645
pubmed: 33087569
Cell. 2015 Nov 19;163(5):1095-1107
pubmed: 26553503
Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):13898-903
pubmed: 26504196
Front Immunol. 2014 Apr 01;5:140
pubmed: 24744762
PLoS Negl Trop Dis. 2019 Feb 7;13(2):e0007042
pubmed: 30730897
J Gen Virol. 2015 Sep;96(9):2483-2500
pubmed: 26219641
J Clin Invest. 2008 Nov;118(11):3738-50
pubmed: 18949059
PLoS Pathog. 2013;9(4):e1003312
pubmed: 23637602
J Interferon Cytokine Res. 2006 Nov;26(11):804-19
pubmed: 17115899
J Immunol. 1989 Oct 15;143(8):2595-601
pubmed: 2507634
J Virol. 2013 Sep;87(18):10255-62
pubmed: 23864626
Lancet Infect Dis. 2010 Oct;10(10):712-22
pubmed: 20883967
Nature. 2018 May;557(7706):570-574
pubmed: 29769725
Cell. 2018 Nov 15;175(5):1198-1212.e12
pubmed: 30293866
Infect Immun. 1982 Jun;36(3):1036-41
pubmed: 6284641
Am J Trop Med Hyg. 1957 Nov;6(6):1017-23
pubmed: 13487974
Cell Rep. 2015 Dec 22;13(11):2553-2564
pubmed: 26686638
Emerg Infect Dis. 2013 Nov;19(11):1839-42
pubmed: 24210165
J Virol. 2006 Dec;80(24):12149-59
pubmed: 17035317
J Clin Virol. 2018 Jan;98:1-4
pubmed: 29172075
J Virol. 1997 Feb;71(2):1558-66
pubmed: 8995682
J Virol. 1996 Mar;70(3):2069-73
pubmed: 8627739
Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):13703-13707
pubmed: 29203665
Am J Trop Med Hyg. 1980 Jul;29(4):638-42
pubmed: 6157332
Nat Immunol. 2016 Sep;17(9):1102-8
pubmed: 27339099
PLoS Negl Trop Dis. 2014 Aug 07;8(8):e2969
pubmed: 25101995
Sci Immunol. 2019 Feb 22;4(32):
pubmed: 30796092
Cell Host Microbe. 2020 Nov 11;28(5):699-711.e7
pubmed: 32783883
Nature. 2020 Dec;588(7837):308-314
pubmed: 33208938
J Exp Med. 2019 Oct 7;216(10):2282-2301
pubmed: 31337735
J Exp Med. 2015 Aug 24;212(9):1361-9
pubmed: 26282878
Cell Host Microbe. 2018 May 9;23(5):672-685.e6
pubmed: 29746837
Nature. 2020 Dec;588(7838):485-490
pubmed: 33032297
Emerg Infect Dis. 2009 Nov;15(11):1830-2
pubmed: 19891877
Nat Rev Immunol. 2020 Oct;20(10):633-643
pubmed: 32782358
J Immunol. 2001 Apr 1;166(7):4697-704
pubmed: 11254730
J Immunol. 2010 May 15;184(10):5903-13
pubmed: 20404274
Nat Immunol. 2018 Nov;19(11):1248-1256
pubmed: 30323338
MAbs. 2017 Jul;9(5):767-773
pubmed: 28463043
Cell. 2020 Aug 20;182(4):901-918.e18
pubmed: 32668198
Methods Mol Biol. 2014;1140:145-57
pubmed: 24590715
J Immunol Methods. 2016 Nov;438:67-70
pubmed: 27600311
J Infect Dis. 2017 Mar 1;215(5):781-785
pubmed: 28039355
Am J Trop Med Hyg. 1981 May;30(3):674-81
pubmed: 6266263
Nat Commun. 2020 Jun 5;11(1):2842
pubmed: 32503971
Sci Rep. 2018 Jan 30;8(1):1860
pubmed: 29382880
Nat Rev Immunol. 2018 Jan;18(1):46-61
pubmed: 29063907
Cell Host Microbe. 2018 Sep 12;24(3):417-428.e5
pubmed: 30146390
EMBO Rep. 2018 Feb;19(2):206-224
pubmed: 29282215
Science. 1988 Jan 29;239(4839):476-81
pubmed: 3277268
Cell Host Microbe. 2015 Jul 8;18(1):86-95
pubmed: 26159721
Protein Sci. 2018 Jan;27(1):14-25
pubmed: 28710774