{"doi":"10.1101/2022.06.09.495439","title":"Nanobody-mediated Complement Activation to Kill HIV-infected Cells","abstract":"Abstract 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303546,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":932557,"name":"Dennis Pedersen","orcid":"0000-0003-1058-2377","position":1,"is_corresponding":false},{"id":844628,"name":"Mikael Winkler","orcid":"0000-0003-0675-7824","position":2,"is_corresponding":false},{"id":995710,"name":"Heidi Gytz Olesen","orcid":"0000-0003-4870-9214","position":3,"is_corresponding":false},{"id":550659,"name":"Ole S. Søgaard","orcid":"0000-0001-9107-2023","position":4,"is_corresponding":false},{"id":845928,"name":"Lars Østergaard","orcid":"0000-0003-2459-0511","position":5,"is_corresponding":false},{"id":995711,"name":"N.S. Laursen","orcid":"0000-0002-7512-2649","position":6,"is_corresponding":false},{"id":996021,"name":"Anna Andersen","orcid":null,"position":7,"is_corresponding":false},{"id":613848,"name":"Martin Tolstrup","orcid":"0000-0001-7020-5173","position":8,"is_corresponding":false},{"id":995709,"name":"Maria Lange Pedersen","orcid":"0000-0003-4338-2507","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T00:32:24.307938Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}