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Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased affinity to Fcγ receptors during acute SHIV AD8-EO infection.

Authors :
Dias J
Fabozzi G
Fourati S
Chen X
Liu C
Ambrozak DR
Ransier A
Laboune F
Hu J
Shi W
March K
Maximova AA
Schmidt SD
Samsel J
Talana CA
Ernste K
Ko SH
Lucas ME
Radecki PE
Boswell KL
Nishimura Y
Todd JP
Martin MA
Petrovas C
Boritz EA
Doria-Rose NA
Douek DC
Sékaly RP
Lifson JD
Asokan M
Gama L
Mascola JR
Pegu A
Koup RA
Source :
Nature communications [Nat Commun] 2024 Aug 29; Vol. 15 (1), pp. 7461. Date of Electronic Publication: 2024 Aug 29.
Publication Year :
2024

Abstract

Anti-HIV-1 broadly neutralizing antibodies (bNAbs) have the dual potential of mediating virus neutralization and antiviral effector functions through their Fab and Fc domains, respectively. So far, bNAbs with enhanced Fc effector functions in vitro have only been tested in NHPs during chronic simian-HIV (SHIV) infection. Here, we investigate the effects of administering in acute SHIV <subscript>AD8-EO</subscript> infection either wild-type (WT) bNAbs or bNAbs carrying the S239D/I332E/A330L (DEL) mutation, which increases binding to FcγRs. Emergence of virus in plasma and lymph nodes (LNs) was delayed by bNAb treatment and occurred earlier in monkeys given DEL bNAbs than in those given WT bNAbs, consistent with faster clearance of DEL bNAbs from plasma. DEL bNAb-treated monkeys had higher levels of circulating virus-specific IFNγ single-producing CD8 <superscript>+</superscript> CD69 <superscript>+</superscript> T cells than the other groups. In LNs, WT bNAbs were evenly distributed between follicular and extrafollicular areas, but DEL bNAbs predominated in the latter. At week 8 post-challenge, LN monocytes and NK cells from DEL bNAb-treated monkeys upregulated proinflammatory signaling pathways and LN T cells downregulated TNF signaling via NF-κB. Overall, bNAbs with increased affinity to FcγRs shape innate and adaptive cellular immunity, which may be important to consider in future strategies of passive bNAb therapy.<br /> (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Details

Language :
English
ISSN :
2041-1723
Volume :
15
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
39198422
Full Text :
https://doi.org/10.1038/s41467-024-51848-y