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

Authors

• Joana Dias, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Giulia Fabozzi, Tissue Analysis Core, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Slim Fourati, Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
• Xuejun Chen, Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Cuiping Liu, Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• David R. Ambrozak, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Amy Ransier, Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Farida Laboune, Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Jianfei Hu, Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Wei Shi, Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Kylie March, Tissue Analysis Core, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Anna A. Maximova, Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Stephen D. Schmidt, Humoral Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Jakob Samsel, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Chloe A. Talana, Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Keenan Ernste, Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Sung Hee Ko, Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Margaret E. Lucas, Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Pierce E. Radecki, Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Kristin L. Boswell, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Yoshiaki Nishimura, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• John-Paul Todd, Translational Research Program, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Malcolm A. Martin, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Constantinos Petrovas, Tissue Analysis Core, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Eli A. Boritz, Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Nicole A. Doria-Rose, Humoral Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Daniel C. Douek, Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Rafick-Pierre Sékaly, Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
• Jeffrey D. Lifson, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
• Mangaiarkarasi Asokan, Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Lucio Gama, Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• John R. Mascola, ModeX Therapeutics, Weston, MA, USA.

Document Type

Journal Article

Publication Date

8-29-2024

Journal

Nature communications

Volume

15

Issue

1

DOI

10.1038/s41467-024-51848-y

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 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 CD69 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.

APA Citation

Dias, Joana; Fabozzi, Giulia; Fourati, Slim; Chen, Xuejun; Liu, Cuiping; Ambrozak, David R.; Ransier, Amy; Laboune, Farida; Hu, Jianfei; Shi, Wei; March, Kylie; Maximova, Anna A.; Schmidt, Stephen D.; Samsel, Jakob; Talana, Chloe A.; Ernste, Keenan; Ko, Sung Hee; Lucas, Margaret E.; Radecki, Pierce E.; Boswell, Kristin L.; Nishimura, Yoshiaki; Todd, John-Paul; Martin, Malcolm A.; Petrovas, Constantinos; Boritz, Eli A.; Doria-Rose, Nicole A.; Douek, Daniel C.; Sékaly, Rafick-Pierre; Lifson, Jeffrey D.; Asokan, Mangaiarkarasi; Gama, Lucio; and Mascola, John R., "Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased affinity to Fcγ receptors during acute SHIV infection" (2024). GW Authored Works. Paper 5418.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5418

Department

Microbiology, Immunology, and Tropical Medicine