Nanobody-mediated Complement Activation to Kill HIV-infected Cells

• DOI: 10.1101/2022.06.09.495439
• Publication Date: 2022-06-12T04:50:11Z
• Authors: Maria Lange Pedersen; Dennis Vestergaar...; Mikael Becher Lyk...; Heidi Gytz Olesen; Ole Schmeltz Søgaard; Lars Østergaard; Nick Stub Laursen; Anna Halling Folk...; Martin Tolstrup
• Keywords: Complement control protein; Complement; Raji cell

Abstract The complement system which is part of the innate immune response against invading pathogens, represents a powerful mechanism for killing infected cells. Utilizing direct recruitment complement-mediated elimination HIV-1-infected cells underexplored. We developed novel therapeutic modality to activity surface This bispecific engager (BiCE) comprised nanobody recruiting complement-initiating protein C1q, and single-chain variable fragments broadly neutralizing antibodies (bNAbs) targeting HIV-1 envelope (Env) protein. Here, we show that two anti-HIV BiCEs V3 loop CD4 binding site, respectively, increase C3 deposition mediate complement-dependent cytotoxicity (CDC) Env expressing Raji Furthermore, trigger activation on primary T with laboratory-adapted strain facilitates over time. In summary, present approach leading these