ArticleJCI insight2019
C4BP-IgM protein as a therapeutic approach to treat Neisseria gonorrhoeae infections.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- C4BP occludes the non-opsonic interaction ofInfection and immunity · 2026Article
- Perspective on the pathogenic Neisseria: milestones, challenges, and future directions.NPJ vaccines · 2026Review
- Gonococcal outer membrane vesicle vaccines: bacterial population biology, clinical trials, immune profiling, and vaccine design.NPJ vaccines · 2026Review
- C4BP occludes the non-opsonic interaction ofbioRxiv : the preprint server for biology · 2026Article
- Pre-clinical efficacy of a C4BP hexameric IgG Fc fusion protein against Neisseria gonorrhoeae.PloS one · 2026Article
- Biologic drug development for treatment and prevention of sexually transmitted infections.Clinical microbiology reviews · 2025Review
- Terminal complement complexes with or without C9 potentiate antimicrobial activity againstmBio · 2025Article
- Acinetobacter baumannii Clinical Isolates Resist Complement-Mediated Lysis by Inhibiting the Complement Cascade and Improperly Depositing MAC.Journal of innate immunity · 2025Article
- A Meta-analysis to Quantify the Risk of Disseminated Gonococcal Infection With Porin B Serotype.Open forum infectious diseases · 2024Article
- Gonococcal PorB: a multifaceted modulator of host immune responses.Trends in microbiology · 2024Review
- C4b-Binding Protein and Factor H Attenuate NLRP3 Inflammasome-Mediated Signalling Response during Group A Streptococci Infection in Human Cells.Journal of innate immunity · 2024Article
- Diverse Functions of C4b-Binding Protein in Health and Disease.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Recruitment of C4b-binding protein is not a complement evasion strategy employed byMicrobiology (Reading, England) · 2023Article
- Bacterium of one thousand and one variants: genetic diversity ofMicrobial genomics · 2023Review
- Vertebrate and Invertebrate Animal and New In Vitro Models for StudyingPathogens (Basel, Switzerland) · 2023Review
- Functional characterization of the gonococcal polyphosphate pseudo-capsule.PLoS pathogens · 2023Article
- Neisseria gonorrhoeae co-opts C4b-binding protein to enhance complement-independent survival from neutrophils.PLoS pathogens · 2023Article
- Immune responses toFrontiers in immunology · 2023Review
- Clinical Isolates ofFrontiers in immunology · 2022Article
- An optimized Factor H-Fc fusion protein against multidrug-resistantFrontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Gonorrhea is a sexually transmitted infection with 87 million new cases per year globally. Increasing antibiotic resistance has severely limited treatment options. A mechanism that Neisseria gonorrhoeae uses to evade complement attack is binding of the complement inhibitor C4b-binding protein (C4BP). We screened 107 porin B1a (PorB1a) and 83 PorB1b clinical isolates randomly selected from a Swedish strain collection over the last 10 years and noted that 96/107 (89.7%) PorB1a and 16/83 (19.3%) PorB1b bound C4BP; C4BP binding substantially correlated with the ability to evade complement-dependent killing (r = 0.78). We designed 2 chimeric proteins that fused C4BP domains to the backbone of IgG or IgM (C4BP-IgG; C4BP-IgM) with the aim of enhancing complement activation and killing of gonococci. Both proteins bound gonococci (KD C4BP-IgM = 2.4 nM; KD C4BP-IgG 980.7 nM), but only hexameric C4BP-IgM efficiently outcompeted heptameric C4BP from the bacterial surface, resulting in enhanced complement deposition and bacterial killing. Furthermore, C4BP-IgM substantially attenuated the duration and burden of colonization of 2 C4BP-binding gonococcal isolates but not a non-C4BP-binding strain in a mouse vaginal colonization model using human factor H/C4BP-transgenic mice. Our preclinical data present C4BP-IgM as an adjunct to conventional antimicrobials for the treatment of gonorrhea.
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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.