Across Functional Boundaries: Making Nonneutralizing Antibodies To Neutralize HIV-1 and Mediate Fc-Mediated Effector Killing of Infected Cells.
ADCC
Ab-CD4 hybrids
HIV-1
neutralization
nonneutralizing antibodies
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
26 10 2021
26 10 2021
Historique:
pubmed:
29
9
2021
medline:
20
1
2022
entrez:
28
9
2021
Statut:
ppublish
Résumé
In HIV-1 infection, many antibodies (Abs) are elicited to Envelope (Env) epitopes that are conformationally masked in the native trimer and are only available for antibody recognition after the trimer binds host cell CD4. Among these are epitopes within the Co-Receptor Binding Site (CoRBS) and the constant region 1 and 2 (C1-C2 or cluster A region). In particular, C1-C2 epitopes map to the gp120 face interacting with gp41 in the native, "closed" Env trimer present on HIV-1 virions or expressed on HIV-1-infected cells. Antibodies targeting this region are therefore nonneutralizing and their potential as mediators of antibody-dependent cellular cytotoxicity (ADCC) of HIV-1-infected cells diminished by a lack of available binding targets. Here, we present the design of Ab-CD4 chimeric proteins that consist of the Ab-IgG1 of a CoRBS or cluster A specificity to the extracellular domains 1 and 2 of human CD4. Our Ab-CD4 hybrids induce potent ADCC against infected primary CD4
Identifiants
pubmed: 34579568
doi: 10.1128/mBio.01405-21
pmc: PMC8546553
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
CD4 Antigens
0
Epitopes
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
e0140521Subventions
Organisme : NIAID NIH HHS
ID : P01 AI150471
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI129769
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150322
Pays : United States
Organisme : NIGMS NIH HHS
ID : P01 GM056550
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI120756
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116274
Pays : United States
Organisme : CIHR
ID : 352417
Pays : Canada
Organisme : NIAID NIH HHS
ID : U01 AI150741
Pays : United States
Références
J Virol. 2014 Nov;88(21):12895-906
pubmed: 25165110
J Virol. 2015 Sep;89(17):8840-54
pubmed: 26085162
EBioMedicine. 2015 Dec 09;3:122-134
pubmed: 26870823
J Virol. 2015 Jan;89(1):545-51
pubmed: 25339767
J Virol. 2014 Jun;88(11):6031-46
pubmed: 24623433
BMC Biol. 2020 Jul 21;18(1):91
pubmed: 32693837
J Virol. 2014 Mar;88(5):2633-44
pubmed: 24352444
Viruses. 2019 Jan 16;11(1):
pubmed: 30654465
Curr Opin HIV AIDS. 2020 Sep;15(5):300-308
pubmed: 32769632
PLoS Pathog. 2015 Mar 25;11(3):e1004772
pubmed: 25807494
Nature. 1996 Nov 14;384(6605):184-7
pubmed: 8906796
Retrovirology. 2010 Feb 16;7:11
pubmed: 20158904
Sci Rep. 2016 Nov 09;6:36685
pubmed: 27827447
Science. 1996 Jun 28;272(5270):1955-8
pubmed: 8658171
J Virol. 2020 Dec 9;:
pubmed: 33298541
mBio. 2018 Mar 20;9(2):
pubmed: 29559570
J Virol. 2014 Jun;88(12):6542-55
pubmed: 24696475
Cell. 1996 Jun 28;85(7):1149-58
pubmed: 8674120
Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6425-30
pubmed: 24733916
mBio. 2020 May 26;11(3):
pubmed: 32457241
J Virol. 2003 Mar;77(5):2859-65
pubmed: 12584309
Proc Natl Acad Sci U S A. 2002 May 14;99(10):6913-8
pubmed: 11997472
Nature. 2009 Apr 2;458(7238):636-40
pubmed: 19287373
J Infect Dis. 2012 Aug 1;206(3):431-41
pubmed: 22634875
J Virol. 2019 May 15;93(11):
pubmed: 30894474
PLoS One. 2017 Mar 27;12(3):e0174550
pubmed: 28346521
Biochemistry. 2004 Feb 17;43(6):1410-7
pubmed: 14769016
Cell. 1996 Jun 28;85(7):1135-48
pubmed: 8674119
Nat Struct Biol. 1995 Dec;2(12):1075-82
pubmed: 8846219
Cell Host Microbe. 2019 Apr 10;25(4):578-587.e5
pubmed: 30974085
Trends Microbiol. 2018 Apr;26(4):253-265
pubmed: 29162391
Virology. 2003 Oct 10;315(1):124-34
pubmed: 14592765
Proc Natl Acad Sci U S A. 1988 Aug;85(16):5879-83
pubmed: 3045807
J Virol. 2015 Dec 30;90(6):2993-3002
pubmed: 26719277
EMBO J. 1997 Feb 17;16(4):695-705
pubmed: 9049299
Nature. 1998 Jun 18;393(6686):648-59
pubmed: 9641677
EBioMedicine. 2016 Oct;12:208-218
pubmed: 27633463
J Virol. 1993 Jul;67(7):3978-88
pubmed: 7685405
J Virol. 2019 Jan 17;93(3):
pubmed: 30429344
J Exp Med. 2005 May 2;201(9):1407-19
pubmed: 15867093
J Virol. 2013 Apr;87(7):4103-11
pubmed: 23345516
Proc Natl Acad Sci U S A. 2015 May 19;112(20):E2687-94
pubmed: 25941367
J Virol. 2015 Dec 04;90(4):2127-34
pubmed: 26637462
J Virol. 2019 Oct 29;93(22):
pubmed: 31484748
Nature. 1996 Nov 14;384(6605):179-83
pubmed: 8906795
J Vis Exp. 2014 Sep 14;(91):51995
pubmed: 25286159
PLoS Pathog. 2013 Sep;9(9):e1003618
pubmed: 24068931
J Virol. 2011 Jul;85(14):7029-36
pubmed: 21543485
Science. 1996 May 10;272(5263):872-7
pubmed: 8629022
Nature. 1997 May 22;387(6631):426-30
pubmed: 9163431
AIDS Res Hum Retroviruses. 2002 Nov 1;18(16):1207-17
pubmed: 12487827
Nature. 2015 Mar 5;519(7541):87-91
pubmed: 25707797
Structure. 2016 May 3;24(5):697-709
pubmed: 27041594
Nature. 1996 Jun 20;381(6584):661-6
pubmed: 8649511
Structure. 2017 Nov 7;25(11):1719-1731.e4
pubmed: 29056481
J Virol Methods. 2015 Apr;215-216:37-44
pubmed: 25712564
Nature. 1990 Nov 1;348(6296):69-73
pubmed: 2172833
Mol Cell. 2010 Mar 12;37(5):656-67
pubmed: 20227370
Microorganisms. 2020 May 11;8(5):
pubmed: 32403312
Science. 1987 Sep 11;237(4820):1351-5
pubmed: 3629244
Science. 2014 Nov 7;346(6210):759-63
pubmed: 25298114
J Virol. 2015 Oct;89(20):10648-55
pubmed: 26269175
Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):E69-78
pubmed: 23237851
AIDS Res Hum Retroviruses. 1996 Feb 10;12(3):191-4
pubmed: 8835195
Nature. 1996 Jun 20;381(6584):667-73
pubmed: 8649512
J Virol Methods. 2014 Nov;208:107-14
pubmed: 25125129
Virology. 2018 Feb;515:38-45
pubmed: 29248757