Engaging an HIV vaccine target through the acquisition of low B cell affinity.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 08 2023
28 08 2023
Historique:
received:
07
12
2021
accepted:
16
08
2023
medline:
31
8
2023
pubmed:
29
8
2023
entrez:
28
8
2023
Statut:
epublish
Résumé
Low affinity is common for germline B cell receptors (BCR) seeding development of broadly neutralizing antibodies (bnAbs) that engage hypervariable viruses, including HIV. Antibody affinity selection is also non-homogenizing, insuring the survival of low affinity B cell clones. To explore whether this provides a natural window for expanding human B cell lineages against conserved vaccine targets, we deploy transgenic mice mimicking human antibody diversity and somatic hypermutation (SHM) and immunize with simple monomeric HIV glycoprotein envelope immunogens. We report an immunization regimen that focuses B cell memory upon the conserved CD4 binding site (CD4bs) through both conventional affinity maturation and reproducible expansion of low affinity BCR clones with public patterns in SHM. In the latter instance, SHM facilitates target acquisition by decreasing binding strength. This suggests that permissive B cell selection enables the discovery of antibody epitopes, in this case an HIV bnAb site.
Identifiants
pubmed: 37640732
doi: 10.1038/s41467-023-40918-2
pii: 10.1038/s41467-023-40918-2
pmc: PMC10462694
doi:
Substances chimiques
AIDS Vaccines
0
Receptors, Antigen, B-Cell
0
Broadly Neutralizing Antibodies
0
HIV Antigens
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
5249Subventions
Organisme : NIAID NIH HHS
ID : R01 AI153098
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI155447
Pays : United States
Organisme : NIDA NIH HHS
ID : DP2 DA042422
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI124378
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137057
Pays : United States
Informations de copyright
© 2023. Springer Nature Limited.
Références
Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):E2567-75
pubmed: 24821781
Nat Immunol. 2009 Apr;10(4):385-93
pubmed: 19252490
J Virol. 2014 Mar;88(5):2645-57
pubmed: 24352455
Immunity. 2018 Jan 16;48(1):174-184.e9
pubmed: 29343437
Front Immunol. 2021 Sep 09;12:730471
pubmed: 34566992
Cell. 2016 Sep 8;166(6):1471-1484.e18
pubmed: 27610571
Science. 2016 Mar 25;351(6280):1458-63
pubmed: 27013733
Nat Nanotechnol. 2020 Aug;15(8):716-723
pubmed: 32601450
Nature. 2022 Sep;609(7929):998-1004
pubmed: 36131022
Science. 2016 Mar 4;351(6277):1048-54
pubmed: 26912368
Cell Rep Med. 2023 Apr 18;4(4):101003
pubmed: 37044090
PLoS Pathog. 2013 Jan;9(1):e1003106
pubmed: 23300456
Cell Rep. 2015 Dec 29;13(12):2842-50
pubmed: 26711348
J Exp Med. 2017 Sep 4;214(9):2573-2590
pubmed: 28847869
Immunity. 2020 Dec 15;53(6):1230-1244.e5
pubmed: 33096040
Cell. 2015 Jun 18;161(7):1505-15
pubmed: 26091035
Sci Rep. 2016 Oct 31;6:36298
pubmed: 27796362
F1000Res. 2013 Apr 03;2:103
pubmed: 24555054
Science. 2016 Sep 30;353(6307):1557-1560
pubmed: 27608668
Theor Biol Med Model. 2014 Jul 03;11:30
pubmed: 24992938
Cell. 2019 Dec 12;179(7):1636-1646.e15
pubmed: 31787378
Front Immunol. 2017 Oct 27;8:1407
pubmed: 29163486
Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):E6639-E6648
pubmed: 27702895
Front Immunol. 2014 Apr 22;5:170
pubmed: 24795717
Immunol Cell Biol. 1998 Aug;76(4):373-81
pubmed: 9723780
Cell Rep. 2020 Aug 25;32(8):108065
pubmed: 32846123
Cold Spring Harb Perspect Biol. 2018 Jan 2;10(1):
pubmed: 28320754
J Virol. 2012 Jul;86(14):7588-95
pubmed: 22573869
Annu Rev Immunol. 2020 Apr 26;38:673-703
pubmed: 32340576
Cell. 2016 Sep 8;166(6):1459-1470.e11
pubmed: 27610570
Sci Transl Med. 2019 Oct 30;11(516):
pubmed: 31666399
Sci Immunol. 2018 Aug 17;3(26):
pubmed: 30120121
mBio. 2019 Feb 26;10(1):
pubmed: 30808695
Retrovirology. 2018 Jul 28;15(1):53
pubmed: 30055635
Proc Natl Acad Sci U S A. 2016 Nov 8;113(45):E7039-E7048
pubmed: 27791170
Front Immunol. 2012 Dec 17;3:383
pubmed: 23251137
Nat Med. 2007 Sep;13(9):1032-4
pubmed: 17721546
J Virol. 2014 Dec;88(24):14002-16
pubmed: 25253346
Nat Protoc. 2016 Feb;11(2):193-213
pubmed: 26741406
Nat Rev Immunol. 2019 Feb;19(2):77-78
pubmed: 30560910
Sci Transl Med. 2018 Jul 4;10(448):
pubmed: 29973404
Science. 2011 Sep 16;333(6049):1593-602
pubmed: 21835983
Nat Rev Immunol. 2023 Mar;23(3):142-158
pubmed: 35962033
Cell. 2015 Jun 4;161(6):1280-92
pubmed: 26004070
Science. 2019 Dec 6;366(6470):
pubmed: 31806786
PLoS One. 2018 Jan 10;13(1):e0190982
pubmed: 29320559
J Virol. 2022 Aug 24;96(16):e0062722
pubmed: 35924923
Annu Rev Immunol. 2012;30:429-57
pubmed: 22224772
Immunity. 2018 Aug 21;49(2):301-311.e5
pubmed: 30076101
Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5663-8
pubmed: 22451932
BMC Bioinformatics. 2012 Feb 14;13:31
pubmed: 22333067
Cell. 2020 Jan 9;180(1):92-106.e11
pubmed: 31866068
J Virol. 2009 Jan;83(2):1045-59
pubmed: 19004942
Cell. 2015 Feb 12;160(4):785-797
pubmed: 25662010
Mol Biol Evol. 2011 Oct;28(10):2731-9
pubmed: 21546353
Proc Natl Acad Sci U S A. 2018 May 1;115(18):4743-4748
pubmed: 29666227
J Virol. 2013 Nov;87(22):12471-80
pubmed: 24027321
Science. 2022 Dec 2;378(6623):eadd6502
pubmed: 36454825
BMC Infect Dis. 2019 Feb 14;19(1):164
pubmed: 30764767
Curr Protoc Mol Biol. 2014 Jul 01;107:4.22.1-4.22.17
pubmed: 24984854
Science. 2011 Sep 16;333(6049):1633-7
pubmed: 21764753
J Immunol. 2017 Feb 1;198(3):1047-1055
pubmed: 28011932
Cell Syst. 2020 Dec 16;11(6):573-588.e9
pubmed: 33031741
Proc Natl Acad Sci U S A. 2020 Sep 15;117(37):22920-22931
pubmed: 32873644
Immunogenetics. 2018 Mar;70(3):143-158
pubmed: 29260260
Science. 2019 Feb 8;363(6427):649-654
pubmed: 30573546
Nature. 2012 Sep 27;489(7417):566-70
pubmed: 22932267
Immunity. 2016 Sep 20;45(3):471-482
pubmed: 27653600
Vaccines (Basel). 2021 Feb 05;9(2):
pubmed: 33562627
J Clin Invest. 2019 Feb 1;129(2):850-862
pubmed: 30521496
Cell Host Microbe. 2019 Jun 12;25(6):827-835.e6
pubmed: 31104946
Sci Transl Med. 2022 Sep 7;14(661):eabo5598
pubmed: 36070369
Nat Med. 2015 Sep;21(9):1065-70
pubmed: 26301691
Sci Rep. 2018 Nov 8;8(1):16527
pubmed: 30410003
Immunity. 2021 Feb 9;54(2):324-339.e8
pubmed: 33453152
Front Immunol. 2014 Jun 02;5:250
pubmed: 24917864
Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20216-21
pubmed: 19875695
Cell. 2023 Jan 5;186(1):147-161.e15
pubmed: 36565698
Cell. 2021 May 27;184(11):2955-2972.e25
pubmed: 34019795
Genes Dev. 2004 Jan 1;18(1):1-11
pubmed: 14724175
Immunity. 2018 Jan 16;48(1):133-146.e6
pubmed: 29287996
Cell Rep. 2022 Nov 8;41(6):111628
pubmed: 36351401
J Virol. 1991 Nov;65(11):6188-93
pubmed: 1717717
Science. 2014 Dec 12;346(6215):1380-1383
pubmed: 25504724
J Virol. 2018 Mar 28;92(8):
pubmed: 29367243
Mol Biol Evol. 2021 Jun 25;38(7):3022-3027
pubmed: 33892491
J Exp Med. 2018 Jan 2;215(1):77-90
pubmed: 29247044
Sci Immunol. 2021 Dec 10;6(66):eabl5842
pubmed: 34648356
Cell. 2023 Jan 5;186(1):131-146.e13
pubmed: 36565697
Science. 2019 Dec 6;366(6470):
pubmed: 31672916
Immunol Rev. 2017 Jan;275(1):203-216
pubmed: 28133796
Immunity. 2018 Dec 18;49(6):1162-1174.e8
pubmed: 30552024
Annu Rev Biochem. 2000;69:531-69
pubmed: 10966468
Immunity. 2016 Mar 15;44(3):542-552
pubmed: 26948373
Immunity. 2013 Aug 22;39(2):245-58
pubmed: 23911655
Immunity. 2019 Oct 15;51(4):735-749.e8
pubmed: 31563464
Science. 2015 Jul 10;349(6244):156-61
pubmed: 26089355
PLoS Pathog. 2016 Sep 14;12(9):e1005864
pubmed: 27627672
J Clin Microbiol. 2004 Apr;42(4):1782-4
pubmed: 15071049
Vaccine. 2018 Aug 23;36(35):5325-5332
pubmed: 30055967
Nature. 2013 Jul 4;499(7456):102-6
pubmed: 23698367
Science. 2010 Aug 13;329(5993):811-7
pubmed: 20616231
Immunol Rev. 2020 Jul;296(1):120-131
pubmed: 32483855
Nat Commun. 2016 Feb 24;7:10618
pubmed: 26907590
Cell. 2010 Nov 12;143(4):592-605
pubmed: 21074050
Immunity. 2022 Sep 13;55(9):1693-1709.e8
pubmed: 35952670
J Exp Med. 2019 Oct 7;216(10):2316-2330
pubmed: 31345931