HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide.
CP: Immunology
HIV vaccine
antibody-antigen binding
cryo-EM structure
envelope trimer
fusion peptide
glycan hole
immunogen design
reproducible antibody class
site of vulnerability
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
25 07 2023
25 07 2023
Historique:
received:
26
02
2023
revised:
18
04
2023
accepted:
21
06
2023
medline:
31
7
2023
pubmed:
12
7
2023
entrez:
12
7
2023
Statut:
ppublish
Résumé
Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability.
Identifiants
pubmed: 37436899
pii: S2211-1247(23)00766-0
doi: 10.1016/j.celrep.2023.112755
pmc: PMC10491024
mid: NIHMS1920497
pii:
doi:
Substances chimiques
AIDS Vaccines
0
Antibodies, Neutralizing
0
env Gene Products, Human Immunodeficiency Virus
0
HIV Antibodies
0
Peptides
0
Types de publication
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112755Subventions
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA AI005022
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Cell Host Microbe. 2019 Jun 12;25(6):873-883.e5
pubmed: 31194940
Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):17624-9
pubmed: 25422458
PLoS Pathog. 2013 Sep;9(9):e1003618
pubmed: 24068931
Nucleic Acids Res. 2013 Jul;41(Web Server issue):W34-40
pubmed: 23671333
Immunity. 2013 Aug 22;39(2):245-58
pubmed: 23911655
Nat Commun. 2017 Nov 21;8(1):1655
pubmed: 29162799
Protein Sci. 2018 Jan;27(1):293-315
pubmed: 29067766
Nature. 2022 Sep;609(7929):998-1004
pubmed: 36131022
Nature. 1985 Jul 4-10;316(6023):72-4
pubmed: 2989707
Bioinformatics. 2019 Sep 1;35(17):2974-2981
pubmed: 30657870
Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):E4088-97
pubmed: 24106303
Nature. 1985 Jul 4-10;316(6023):69-72
pubmed: 2989706
Nat Struct Mol Biol. 2015 Nov;22(11):833-4
pubmed: 26581513
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Nature. 2014 Nov 6;515(7525):138-42
pubmed: 25186731
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
Immunity. 2014 May 15;40(5):669-80
pubmed: 24768348
Nat Med. 2021 Dec;27(12):2234-2245
pubmed: 34887575
Immunity. 2019 Nov 19;51(5):915-929.e7
pubmed: 31732167
EClinicalMedicine. 2022 Jun 01;48:101477
pubmed: 35783486
Nature. 2012 Nov 15;491(7424):406-12
pubmed: 23151583
J Virol. 2020 Jun 16;94(13):
pubmed: 32295908
Science. 2011 Sep 16;333(6049):1593-602
pubmed: 21835983
Cell. 1986 Jun 6;45(5):637-48
pubmed: 2423250
Nat Methods. 2015 Oct;12(10):943-6
pubmed: 26280328
Vaccine. 2021 Jun 8;39(25):3379-3387
pubmed: 34020817
PLoS Pathog. 2020 Aug 31;16(8):e1008753
pubmed: 32866207
Bioinformatics. 2017 Oct 01;33(19):3051-3057
pubmed: 28582506
J Virol. 2010 Feb;84(3):1439-52
pubmed: 19939925
Nature. 2019 Feb;566(7744):398-402
pubmed: 30760926
Science. 2009 Oct 9;326(5950):285-9
pubmed: 19729618
J Virol. 2017 Jul 27;91(16):
pubmed: 28592540
Cell Rep. 2021 Nov 2;37(5):109922
pubmed: 34731616
Glycobiology. 2019 Apr 1;29(4):320-331
pubmed: 30689864
J Comput Chem. 2008 Aug;29(11):1859-65
pubmed: 18351591
J Virol. 2015 Oct 14;90(1):76-91
pubmed: 26468542
Protein Sci. 2021 Jan;30(1):70-82
pubmed: 32881101
PLoS One. 2019 Apr 17;14(4):e0215163
pubmed: 30995238
Cell Rep. 2020 Nov 24;33(8):108432
pubmed: 33238130
J Mol Biol. 2007 Sep 21;372(3):774-97
pubmed: 17681537
Science. 2016 May 13;352(6287):828-33
pubmed: 27174988
Science. 2011 Sep 16;333(6049):1633-7
pubmed: 21764753
Nat Struct Mol Biol. 2015 Jul;22(7):522-31
pubmed: 26098315
Sci Transl Med. 2022 Sep 7;14(661):eabo5598
pubmed: 36070369
Nat Commun. 2022 Dec 14;13(1):7733
pubmed: 36517467
J Struct Biol. 2005 Oct;152(1):36-51
pubmed: 16182563
J Comput Chem. 2011 Nov 15;32(14):3135-41
pubmed: 21815173
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Structure. 2019 Jan 2;27(1):196-206.e6
pubmed: 30471922
AIDS. 2014 Jan 14;28(2):163-9
pubmed: 24361678
Nat Commun. 2021 Nov 9;12(1):6470
pubmed: 34753907
Clin Chim Acta. 1994 Jan 31;224(2):191-7
pubmed: 8004789
Nature. 2003 Mar 20;422(6929):307-12
pubmed: 12646921
Protein Sci. 2020 Apr;29(4):1069-1078
pubmed: 31730249
Cell Rep. 2020 Oct 27;33(4):108322
pubmed: 33091382
BMC Bioinformatics. 2004 Jun 04;5:69
pubmed: 15180909
J Struct Biol. 2005 Jul;151(1):41-60
pubmed: 15890530
Science. 2015 Jul 10;349(6244):156-61
pubmed: 26089355
PLoS Pathog. 2016 Sep 14;12(9):e1005864
pubmed: 27627672
Nat Methods. 2017 Apr;14(4):331-332
pubmed: 28250466
Cell Rep. 2016 Aug 30;16(9):2327-38
pubmed: 27545891
Cell Rep. 2016 May 31;15(9):1986-99
pubmed: 27210756
Cell. 2015 Dec 17;163(7):1702-15
pubmed: 26687358
Cell Rep. 2017 Apr 25;19(4):719-732
pubmed: 28445724
Cell Rep. 2018 Feb 13;22(7):1798-1809
pubmed: 29444432
Nat Med. 2018 Jun;24(6):857-867
pubmed: 29867235
Cell. 2019 Jul 25;178(3):567-584.e19
pubmed: 31348886
Nature. 2011 Sep 22;477(7365):466-70
pubmed: 21849977
PLoS Pathog. 2015 May 29;11(5):e1004932
pubmed: 26023780
Semin Immunol. 2020 Aug;50:101428
pubmed: 33246736
J Synchrotron Radiat. 2004 Jan 1;11(Pt 1):53-5
pubmed: 14646133
Science. 2010 Aug 13;329(5993):856-61
pubmed: 20616233
MAbs. 2009 Sep-Oct;1(5):439-42
pubmed: 20065632