title: Immunization against a saccharide epitope accelerates clearance of experimental gonococcal infection.
abstract: The emergence of ceftriaxone-resistant strains of Neisseria gonorrhoeae may herald an era of untreatable gonorrhea. Vaccines against this infection are urgently needed. The 2C7 epitope is a conserved oligosaccharide (OS) structure, a part of lipooligosaccharide (LOS) on N gonorrhoeae. The epitope is expressed by 94% of gonococci that reside in the human genital tract (in vivo) and by 95% of first passaged isolates. Absence of the 2C7 epitope shortens the time of gonococcal carriage in a mouse model of genital infection. To circumvent the limitations of saccharide immunogens in producing long lived immune responses, previously we developed a peptide mimic (called PEP1) as an immunologic surrogate of the 2C7-OS epitope and reconfigured it into a multi-antigenic peptide, (MAP1). To test vaccine efficacy of MAP1, female BALB/c mice were passively immunized with a complement-dependent bactericidal monoclonal antibody specific for the 2C7 epitope or were actively immunized with MAP1. Mice immunized with MAP1 developed a TH1-biased anti-LOS IgG antibody response that was also bactericidal. Length of carriage was shortened in immune mice; clearance occurred in 4 days in mice passively administered 2C7 antibody vs. 6 days in mice administered control IgG3λ mAb in one experiment (p = 0.03) and 6 vs. 9 days in a replicate experiment (p = 0.008). Mice vaccinated with MAP1 cleared infection in 5 days vs. 9 days in mice immunized with control peptide (p = 0.0001 and p = 0.0002, respectively in two replicate experiments). Bacterial burden was lower over the course of infection in passively immunized vs. control mice in both experiments (p = 0.008 and p = 0.0005); burdens were also lower in MAP1 immunized mice vs. controls (p<0.0001) and were inversely related to vaccine antibodies induced in the vagina (p = 0.043). The OS epitope defined by mAb 2C7 may represent an effective vaccine target against gonorrhea, which is rapidly becoming incurable with currently available antibiotics.
authors.affiliation: Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Sunita
authors.initials: S
authors.lastname: Gulati
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.forename: George W
authors.initials: GW
authors.lastname: Reed
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Su
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cox
authors.forename: Frank
authors.initials: F
authors.lastname: St Michael
authors.forename: Jacek
authors.initials: J
authors.lastname: Stupak
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lewis
authors.forename: Sanjay
authors.initials: S
authors.lastname: Ram
authors.forename: Peter A
authors.initials: PA
authors.lastname: Rice
mesh_terms: D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000494:pharmacology*; D001428:Bacterial Vaccines / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D006069:Gonorrhea / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009344:Neisseria gonorrhoeae / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D000907:Antibodies, Bacterial; D058846:Antibodies, Monoclonal, Murine-Derived; D001428:Bacterial Vaccines; D000939:Epitopes; D007074:Immunoglobulin G; D010455:Peptides; D011135:Polysaccharides, Bacterial