ArticlePLoS biology2019
Complement alone drives efficacy of a chimeric antigonococcal monoclonal antibody.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- C1q as a target molecule to treat human disease: What do mouse studies teach us?Frontiers in immunology · 2022Pooled it
- Preclinical Evaluation of Novel ConservedVaccines · 2026Article
- An antibody-drug conjugate active against antibiotic-resistantProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Complement protein concentrations and activity in human cervical mucus.bioRxiv : the preprint server for biology · 2026Article
- An mRNA-Lipid Nanoparticle Platform Encoding the Conserved Outer Membrane Protein BamA Elicits Broadly Cross-Reactive Systemic and Mucosal Antibodies Against Antimicrobial-ResistantbioRxiv : the preprint server for biology · 2026Article
- Review
- Improvement in binding and function of a monoclonal antibody against Shigella flexneri 3a O-antigen via phage display and whole-cell in-solution panning.The Journal of biological chemistry · 2026Article
- MtrE Loop2-specific multiple antigenic peptide vaccine and monoclonal antibody confer complement-dependent protection against Neisseria gonorrhoeae.NPJ vaccines · 2026Article
- Biology of novel LpxC inhibitors forMicrobiology spectrum · 2026Article
- Pre-clinical efficacy of a C4BP hexameric IgG Fc fusion protein against Neisseria gonorrhoeae.PloS one · 2026Article
- Review
- Review
- Evaluation of Immunization Route in Induction of Vaccine-Mediated Anti-Gonococcal Immune Responses in a Murine Model of Ascending Infection.The Journal of infectious diseases · 2025Article
- Structure-based engineering of a nutrient acquisition protein enhances neutralizing antibodies and protection for the development of a gonococcal vaccine.bioRxiv : the preprint server for biology · 2025Article
- Contribution of the different Neisseria gonorrhoeae lipooligosaccharide structural variants to functional responses elicited by GMMA outer membrane vesicles.NPJ vaccines · 2025Article
- Isotype conversion of Staphylococcal-specific IgG into IgM broadens the reactivity to other bacterial pathogens.Cell reports. Medicine · 2025Article
- Biologic drug development for treatment and prevention of sexually transmitted infections.Clinical microbiology reviews · 2025Review
- Interferon-epsilon, an estrogen-induced type I interferon, is uniquely exploited by Neisseria gonorrhoeae via effects on sialic acid metabolism.Cell host & microbe · 2025Article
- A novel GMMA-based gonococcal vaccine demonstrates functional immune responses in mice.NPJ vaccines · 2025Article
- Terminal complement complexes with or without C9 potentiate antimicrobial activity againstmBio · 2025Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 7 institutions in 4 countries.
Funding
Abstract
Multidrug-resistant Neisseria gonorrhoeae is a global health problem. Monoclonal antibody (mAb) 2C7 recognizes a gonococcal lipooligosaccharide epitope that is expressed by >95% of clinical isolates and hastens gonococcal vaginal clearance in mice. Chimeric mAb 2C7 (human immunoglobulin G1 [IgG1]) with an E430G Fc modification that enhances Fc:Fc interactions and hexamerization following surface-target binding and increases complement activation (HexaBody technology) showed significantly greater C1q engagement and C4 and C3 deposition compared to mAb 2C7 with wild-type Fc. Greater complement activation by 2C7-E430G Fc translated to increased bactericidal activity in vitro and, consequently, enhanced efficacy in mice, compared with "Fc-unmodified" chimeric 2C7. Gonococci bind the complement inhibitors factor H (FH) and C4b-binding protein (C4BP) in a human-specific manner, which dampens antibody (Ab)-mediated complement-dependent killing. The variant 2C7-E430G Fc overcame the barrier posed by these inhibitors in human FH/C4BP transgenic mice, for which a single 1 μg intravenous dose cleared established infection. Chlamydia frequently coexists with and exacerbates gonorrhea; 2C7-E430G Fc also proved effective against gonorrhea in gonorrhea/chlamydia-coinfected mice. Complement activation alone was necessary and sufficient for 2C7 function, evidenced by the fact that (1) "complement-inactive" Fc modifications that engaged Fc gamma receptor (FcγR) rendered 2C7 ineffective, nonetheless; (2) 2C7 was nonfunctional in C1q-/- mice, when C5 function was blocked, or in C9-/- mice; and (3) 2C7 remained effective in neutrophil-depleted mice and in mice treated with PMX205, a C5a receptor (C5aR1) inhibitor. We highlight the importance of complement activation for antigonococcal Ab function in the genital tract. Elucidating the correlates of protection against gonorrhea will inform the development of Ab-based gonococcal vaccines and immunotherapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.