{"doi":"10.3389/fimmu.2020.583305","title":"Development of Complement Factor H–Based Immunotherapeutic Molecules in Tobacco Plants Against Multidrug-Resistant Neisseria gonorrhoeae","abstract":"Novel therapeutics against the global threat of multidrug-resistant Neisseria gonorrhoeae (Ng) are urgently needed. Gonococci possess several mechanisms to evade killing by human complement, including binding of factor H (FH), a key inhibitor of the alternative pathway. FH comprises 20 short consensus repeat (SCR) domains organized in a head-to-tail manner as a single chain. N. gonorrhoeae binds two regions in FH; domains 6 and 7 and domains 18 through 20. We designed a novel anti-infective immunotherapeutic molecule that fuses domains 18-20 of FH containing a D-to-G mutation in domain 19 at position 1119 (called FH*) with human IgG1 Fc. FH*/Fc retained binding to gonococci but did not lyse human erythrocytes. Expression of FH*/Fc in tobacco plants was undertaken as an alternative, economical production platform. FH*/Fc was expressed in high yields in tobacco plants (300-600 mg/kg biomass). The activities of plant- and CHO-cell produced FH*/Fc against gonococci were similar in vitro and in the mouse vaginal colonization model of gonorrhea. The addition of flexible linkers [e.g., (GGGGS)2 or (GGGGS)3] between FH* and Fc improved the bactericidal efficacy of FH*/Fc 2.7-fold. The linkers also improved PMN-mediated opsonophagocytosis about 11-fold. FH*/Fc with linker also effectively reduced the duration and burden of colonization of two gonococcal strains tested in mice. FH*/Fc lost efficacy: i) in C6 -/- mice (no terminal complement) and ii) when Fc was mutated to abrogate complement activation, suggesting that an intact complement was necessary for FH*/Fc function in vivo. In summary, plant-produced FH*/Fc represent promising prophylactic or adjunctive immunotherapeutics against multidrug-resistant gonococci.","journal":"Frontiers in Immunology","year":2020,"id":87794,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":445821,"name":"Thi Hai Yen Tran","orcid":"0000-0003-1414-2328","position":1,"is_corresponding":false},{"id":406676,"name":"Bo Zheng","orcid":"0000-0002-2237-2898","position":2,"is_corresponding":false},{"id":445822,"name":"Rosane B. DeOliveira","orcid":"0000-0003-3563-4970","position":3,"is_corresponding":false},{"id":408016,"name":"Sunita Gulati","orcid":null,"position":4,"is_corresponding":false},{"id":445823,"name":"Wen‐Chao Song","orcid":"0009-0004-1740-843X","position":5,"is_corresponding":false},{"id":446536,"name":"James Maclean","orcid":null,"position":6,"is_corresponding":false},{"id":446537,"name":"Keith L. Wycoff","orcid":null,"position":7,"is_corresponding":false},{"id":406677,"name":"Sanjay Ram","orcid":"0000-0003-0058-9532","position":8,"is_corresponding":false},{"id":445820,"name":"Jutamas Shaughnessy","orcid":"0000-0003-0832-9954","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T22:00:29.831859Z","pmid":"33193396","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":[]}