ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Phase-Variable Heptose I Glycan Extensions Modulate Efficacy of 2C7 Vaccine Antibody Directed against Neisseria gonorrhoeae Lipooligosaccharide.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. 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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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, 36 citations in OpenAlex.
- Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.Sexually transmitted diseases · 2019Trial
- Genomic analysis ofMicrobiology spectrum · 2026Article
- Contribution of the different Neisseria gonorrhoeae lipooligosaccharide structural variants to functional responses elicited by GMMA outer membrane vesicles.NPJ vaccines · 2025Article
- Vaginally-delivered fast-dissolving antibody tablets (FDAT) for on-demand non-hormonal contraception and multi-purpose protection.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Isolation of human monoclonal antibodies from 4CMenB vaccinees reveals PorB and LOS as the main OMV components inducing cross-strain protection.Frontiers in immunology · 2025Article
- Review
- Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria.Nature communications · 2024Article
- Article
- Evaluating vaccine-elicited antibody activities againstInfection and immunity · 2023Article
- Comparison of lipooligosaccharides from human challenge strains ofFrontiers in microbiology · 2023Article
- Immune responses toFrontiers in immunology · 2023Review
- Phylogenomic Comparison ofOpen forum infectious diseases · 2022Article
- Article
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- Therapeutic CMP-Nonulosonates against Multidrug-ResistantJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Meningococcal core and accessory phasomes vary by clonal complex.Microbial genomics · 2020Article
- Bypassing Phase Variation of Lipooligosaccharide (LOS): Using Heptose 1 Glycan Mutants To Establish Widespread Efficacy of Gonococcal Anti-LOS Monoclonal Antibody 2C7.Infection and immunity · 2020Article
- Development of Complement Factor H-Based Immunotherapeutic Molecules in Tobacco Plants Against Multidrug-ResistantFrontiers in immunology · 2020Article
- Preclinical Efficacy of a Lipooligosaccharide Peptide Mimic Candidate Gonococcal Vaccine.mBio · 2019Article
- Complement alone drives efficacy of a chimeric antigonococcal monoclonal antibody.PLoS biology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection, gonorrhea, has developed resistance to most conventional antibiotics. Safe and effective vaccines against gonorrhea are needed urgently. A candidate vaccine that targets a lipooligosaccharide (LOS) epitope recognized mAb 2C7 attenuates gonococcal burden in the mouse vaginal colonization model. Glycan extensions from the LOS core heptoses (HepI and HepII) are controlled by phase-variable LOS glycosyltransferase (lgt) genes; we sought to define how HepI glycan extensions affect mAb 2C7 function. Isogenic gonococcal mutants in which the lgt required for mAb 2C7 reactivity (lgtG) was genetically locked on and the lgt loci required for HepI variation (lgtA, lgtC, and lgtD) were genetically locked on or off in different combinations were created. We observed 100% complement-dependent killing by mAb 2C7 of a mutant that expressed lactose (Gal-Glc) from HepI, whereas a mutant that expressed Gal-Gal-Glc-HepI fully resisted killing (>100% survival). Mutants that elaborated 4- (Gal-GlcNAc-Gal-Glc-HepI) and 5-glycan (GalNAc-Gal-GlcNAc-Gal-Glc-HepI) structures displayed intermediate phenotypes (<50% killing with 2 μg/ml and >95% killing with 4 μg/ml mAb 2C7). The contrasting phenotypes of the lactose-HepI and the Gal-Gal-Glc-HepI LOS structures were recapitulated with phase variants of a recently isolated clinical strain. Despite lack of killing of the Gal-Gal-Glc-HepI mutants, mAb 2C7 deposited sufficient C3 on these bacteria for opsonophagocytic killing by human neutrophils. In conclusion, mAb 2C7 showed functional activity against all gonococcal HepI LOS structures defined by various lgtA/C/D on/off combinations, thereby providing further impetus for use of the 2C7 epitope in a gonococcal vaccine.
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