Afucosylated broadly neutralizing antibodies enhance clearance of HIV-1 infected cells through cell-mediated killing.

Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE

Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-

HIV-1*/immunology ; Killer Cells, Natural*/immunology ; HIV Infections*/immunology ; HIV Infections*/virology ; HIV Infections*/drug therapy ; HIV Antibodies*/immunology ; Broadly Neutralizing Antibodies*/immunology; Humans ; Antibodies, Neutralizing/immunology ; Receptors, IgG/immunology ; Receptors, IgG/metabolism ; Antibody-Dependent Cell Cytotoxicity/immunology ; Fucose

Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have the capacity to delay viral rebound when administered to people with HIV-1 (PWH) during anti-retroviral therapy (ART) interruption. To further enhance the performance of bNAbs through their Fc effector functions, in particular NK cell-mediated killing of HIV-1 infected cells, we have produced a panel of glyco-engineered (afucosylated) bNAbs with enhanced affinity for Fc gamma receptor IIIa. These afucosylated anti-HIV-1 bNAbs enhance NK cell activation and degranulation compared to fucosylated counterparts even at low antigen density. NK cells from PWH expressing exhaustion markers PD-1 and TIGIT are activated in a similar fashion by afucosylated bNAbs as NK cell from HIV-1 negative individuals. Killing of HIV-1 infected cells is most effective with afucosylated bNAbs 2G12, N6, PGT151 and PGDM1400, whereas afucosylated PGT121 and non-neutralizing antibody A32 only induce minor NK cell-mediated killing. These data indicate that the approach angle and affinity of Abs influence the capacity to induce antibody-dependent cellular cytotoxicity. Thus, afucosylated bNAbs have the capacity to induce NK cell-mediated killing of infected cells, which warrants further investigation of afucosylated bNAb administration in vivo, aiming for reduction of the viral reservoir and ART free durable control.
(© 2024. The Author(s).)

J Virol. 2017 Sep 27;91(20):. (PMID: 28794022)
Sci Rep. 2022 Nov 3;12(1):18567. (PMID: 36329160)
Science. 2015 Jul 10;349(6244):aac4223. (PMID: 26089353)
Glycoconj J. 2013 Feb;30(2):147-57. (PMID: 22572841)
PLoS Pathog. 2013;9(5):e1003342. (PMID: 23658524)
J Clin Invest. 2022 Dec 15;132(24):. (PMID: 36282589)
J Clin Invest. 2020 Oct 1;130(10):5157-5170. (PMID: 32584790)
AIDS. 2018 Aug 24;32(13):1749-1761. (PMID: 29762173)
Expert Opin Biol Ther. 2021 Feb;21(2):161-181. (PMID: 32933335)
Cell. 2014 Sep 11;158(6):1243-1253. (PMID: 25215485)
Clin Cancer Res. 2007 Mar 15;13(6):1875-82. (PMID: 17363544)
Mol Ther Methods Clin Dev. 2020 Nov 11;20:204-217. (PMID: 33426147)
J Virol. 2021 Aug 25;95(18):e0079621. (PMID: 34232070)
Sci Transl Med. 2021 Jun 2;13(596):. (PMID: 33979301)
J Virol. 1996 Feb;70(2):1100-8. (PMID: 8551569)
Front Immunol. 2022 Mar 16;13:842746. (PMID: 35371060)
J Immunol Methods. 2005 Nov 30;306(1-2):151-60. (PMID: 16219319)
J Immunol. 2010 Dec 1;185(11):6876-82. (PMID: 21041724)
Nature. 2022 Jun;606(7913):368-374. (PMID: 35418681)
mBio. 2018 Mar 20;9(2):. (PMID: 29559570)
Immunity. 2014 May 15;40(5):669-80. (PMID: 24768348)
Nat Med. 2021 Dec;27(12):2085-2098. (PMID: 34848888)
J Virol. 2015 Oct;89(20):10176-89. (PMID: 26223643)
Trends Immunol. 2022 Oct;43(10):800-814. (PMID: 36008258)
Sci Rep. 2016 Nov 22;6:36964. (PMID: 27872474)
mBio. 2019 Dec 17;10(6):. (PMID: 31848282)
Front Immunol. 2017 Aug 02;8:877. (PMID: 28824618)
Nat Commun. 2016 Mar 03;7:10844. (PMID: 26936020)
J Virol. 2017 Nov 14;91(23):. (PMID: 28956765)
J Virol. 2017 Mar 29;91(8):. (PMID: 28122982)
mBio. 2021 Oct 26;12(5):e0140521. (PMID: 34579568)
J Cell Biol. 2018 Sep 3;217(9):2983-2985. (PMID: 30108125)
J Immunol. 2016 Aug 15;197(4):1507-16. (PMID: 27385782)
J Biol Chem. 2017 Mar 3;292(9):3900-3908. (PMID: 28077575)
Nat Commun. 2022 Jan 10;13(1):121. (PMID: 35013215)
Science. 2016 May 20;352(6288):1001-4. (PMID: 27199430)
Curr HIV/AIDS Rep. 2019 Feb;16(1):96-104. (PMID: 30734905)
Front Immunol. 2019 May 10;10:1025. (PMID: 31134085)
Immunity. 2016 Nov 15;45(5):1108-1121. (PMID: 27851912)
Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):17624-9. (PMID: 25422458)
Nature. 2022 Jun;606(7913):375-381. (PMID: 35650437)
J Immunol. 2019 Dec 15;203(12):3126-3135. (PMID: 31748349)
PLoS One. 2015 Mar 27;10(3):e0121788. (PMID: 25816339)
Cell Rep. 2021 Apr 6;35(1):108933. (PMID: 33826885)
Nat Commun. 2022 Oct 29;13(1):6473. (PMID: 36309514)
PLoS Pathog. 2013 Sep;9(9):e1003618. (PMID: 24068931)
Front Immunol. 2022 May 20;13:879124. (PMID: 35720328)
J Virol. 2011 Jul;85(14):7029-36. (PMID: 21543485)
J Nucl Med. 2022 Apr;63(4):629-636. (PMID: 34353869)
Antibodies (Basel). 2020 Nov 17;9(4):. (PMID: 33212886)
MAbs. 2020 Jan-Dec;12(1):1836719. (PMID: 33121334)
J Leukoc Biol. 2023 Feb 1;113(2):109-138. (PMID: 36822173)
J Virol. 2014 Mar;88(5):2489-507. (PMID: 24352443)
J Immunol. 2019 Aug 1;203(3):705-717. (PMID: 31253727)
Cell Rep. 2021 May 25;35(8):109167. (PMID: 34038720)
J Clin Invest. 2013 May;123(5):2183-92. (PMID: 23563315)
Front Immunol. 2022 May 16;13:893648. (PMID: 35651621)
Nat Med. 2022 Nov;28(11):2424-2435. (PMID: 36253609)
Lancet Microbe. 2022 Mar;3(3):e203-e214. (PMID: 35544074)
Nature. 2018 Sep;561(7724):479-484. (PMID: 30258136)
Nature. 2018 Nov;563(7731):360-364. (PMID: 30283138)
J Clin Invest. 2019 Jan 2;129(1):182-191. (PMID: 30475230)
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552. (PMID: 34723319)
Methods Mol Biol. 2017;1503:31-47. (PMID: 27743357)
J Immunol. 2018 Aug 1;201(3):971-981. (PMID: 29934472)
Cell. 2015 Dec 17;163(7):1702-15. (PMID: 26687358)
Science. 2020 Aug 7;369(6504):643-650. (PMID: 32540902)
Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):3485-3490. (PMID: 28289219)
Front Immunol. 2020 Jul 30;11:1635. (PMID: 32849559)
Front Immunol. 2021 Feb 26;12:602492. (PMID: 33717085)
J Virol. 2018 May 29;92(12):. (PMID: 29593039)
Semin Immunol. 2021 Jan;51:101412. (PMID: 32981836)
J Virol. 2012 Jun;86(11):6189-96. (PMID: 22457527)
Clin Transl Immunology. 2021 Oct 19;10(10):e1348. (PMID: 34707863)
Nat Med. 2020 Feb;26(2):222-227. (PMID: 32015556)
J Virol. 2022 Jan 12;96(1):e0155221. (PMID: 34669426)
J Cell Biol. 2018 Sep 3;217(9):3267-3283. (PMID: 29967280)
PLoS Pathog. 2024 Jan 22;20(1):e1011819. (PMID: 38252675)
Front Immunol. 2021 Mar 16;12:641521. (PMID: 33796107)

110425-73-RKRL amfAR, The Foundation for AIDS Research (amfAR)

0 (HIV Antibodies)
0 (Broadly Neutralizing Antibodies)
0 (Antibodies, Neutralizing)
0 (Receptors, IgG)
28RYY2IV3F (Fucose)

Date Created: 20240809 Date Completed: 20240809 Latest Revision: 20241219

20250114

PMC11316088

10.1038/s42003-024-06659-8

39122901