ReviewImmunobiology2016
Utilizing complement evasion strategies to design complement-based antibacterial immunotherapeutics: Lessons from the pathogenic Neisseriae.
Review in Immunobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
24 citing papers in PubMed, 35 citations in OpenAlex.
- Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.Sexually transmitted diseases · 2019Trial
- Recruiting the Immune System against Pathogenic Bacteria Using High-Affinity Chimeric Tags.Bioconjugate chemistry · 2024Article
- Addressing Sexually Transmitted Infections Due toMicroorganisms · 2024Review
- The human factor H protein family - an update.Frontiers in immunology · 2024Review
- Recent advances onSynthetic and systems biotechnology · 2023Review
- Vertebrate and Invertebrate Animal and New In Vitro Models for StudyingPathogens (Basel, Switzerland) · 2023Review
- Microbial evasion of the complement system: a continuous and evolving story.Frontiers in immunology · 2023Review
- Article
- An optimized Factor H-Fc fusion protein against multidrug-resistantFrontiers in immunology · 2022Article
- Hijacking Factor H for Complement Immune Evasion.Frontiers in immunology · 2021Review
- Efficacy of Antigonococcal CMP-Nonulosonate Therapeutics Require Cathelicidins.The Journal of infectious diseases · 2020Article
- Complement Evasion Strategies of Human Pathogenic Bacteria.Indian journal of microbiology · 2020Review
- Therapeutic CMP-Nonulosonates against Multidrug-ResistantJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Cell intrinsic functions of neutrophils and their manipulation by pathogens.Current opinion in immunology · 2019Review
- Role of Gonococcal Neisserial Surface Protein A (NspA) in Serum Resistance and Comparison of Its Factor H Binding Properties with Those of Its Meningococcal Counterpart.Infection and immunity · 2019Article
- Catch Me if You Can: Streptococcus pyogenes Complement Evasion Strategies.Journal of innate immunity · 2019Review
- Antibody-mediated protection against Ebola virus.Nature immunology · 2018Review
- Human Factor H Domains 6 and 7 Fused to IgG1 Fc Are Immunotherapeutic againstJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- Structure-Function Relationships of the Neisserial EptA Enzyme Responsible for Phosphoethanolamine Decoration of Lipid A: Rationale for Drug Targeting.Frontiers in microbiology · 2018Review
- Factor H-IgG Chimeric Proteins as a Therapeutic Approach against the Gram-Positive Bacterial PathogenJournal of immunology (Baltimore, Md. : 1950) · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Novel therapies are urgently needed to combat the global threat of multidrug-resistant pathogens. Complement forms an important arm of innate defenses against infections. In physiological conditions, complement activation is tightly controlled by soluble and membrane-associated complement inhibitors, but must be selectively activated on invading pathogens to facilitate microbial clearance. Many pathogens, including Neisseria gonorrhoeae and N. meningitidis, express glycans, including N-acetylneuraminic acid (Neu5Ac), that mimic host structures to evade host immunity. Neu5Ac is a negatively charged 9-cabon sugar that inhibits complement, in part by enhancing binding of the complement inhibitor factor H (FH) through C-terminal domains (19 and 20) on FH. Other microbes also bind FH, in most instances through FH domains 6 and 7 or 18-20. Here we describe two strategies to target complement activation on Neisseriae. First, microbial binding domains of FH were fused to IgG Fc to create FH18-20/Fc (binds gonococci) and FH6,7/Fc (binds meningococci). A point mutation in FH domain 19 eliminated hemolysis caused by unmodified FH18-20, but retained binding to gonococci. FH18-20/Fc and FH6,7/Fc mediated complement-dependent killing in vitro and showed efficacy in animal models of gonorrhea and meningococcal bacteremia, respectively. The second strategy utilized CMP-nonulosonate (CMP-NulO) analogs of sialic acid that were incorporated into LOS and prevented complement inhibition by physiologic CMP-Neu5Ac and resulted in attenuated gonococcal infection in mice. While studies to establish the safety of these agents are needed, enhancing complement activation on microbes may represent a promising strategy to treat antimicrobial resistant organisms.
Indexed as
Identifiers
What OpenQuestion holds
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.