Nanobody-mediated complement activation to kill HIV-infected cells.

Autor: Pedersen ML; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Pedersen DV; Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark., Winkler MBL; Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark., Olesen HG; Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark., Søgaard OS; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark., Østergaard L; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark., Laursen NS; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Rahimic AHF; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Tolstrup M; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2023 Apr 11; Vol. 15 (4), pp. e16422. Date of Electronic Publication: 2023 Feb 17.
DOI: 10.15252/emmm.202216422
Abstrakt: The complement system which is part of the innate immune response against invading pathogens represents a powerful mechanism for killing of infected cells. Utilizing direct complement recruitment for complement-mediated elimination of HIV-1-infected cells is underexplored. We developed a novel therapeutic modality to direct complement activity to the surface of HIV-1-infected cells. This bispecific complement engager (BiCE) is comprised of a nanobody recruiting the complement-initiating protein C1q, and single-chain variable fragments of broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope (Env) protein. Here, we show that two anti-HIV BiCEs targeting the V3 loop and the CD4 binding site, respectively, increase C3 deposition and mediate complement-dependent cytotoxicity (CDC) of HIV-1 Env-expressing Raji cells. Furthermore, anti-HIV BiCEs trigger complement activation on primary CD4 T cells infected with laboratory-adapted HIV-1 strain and facilitates elimination of HIV-1-infected cells over time. In summary, we present a novel approach to direct complement deposition to the surface of HIV-1-infected cells leading to complement-mediated killing of these cells.
(© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
Externí odkaz: