Immunization against a saccharide epitope accelerates clearance of experimental gonococcal infection

PLoS Pathog. 2013;9(8):e1003559. doi: 10.1371/journal.ppat.1003559. Epub 2013 Aug 29.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Animals
  • Antibodies, Bacterial / immunology
  • Antibodies, Bacterial / pharmacology*
  • Antibodies, Monoclonal, Murine-Derived / immunology
  • Antibodies, Monoclonal, Murine-Derived / pharmacology*
  • Bacterial Vaccines / immunology
  • Bacterial Vaccines / microbiology
  • Disease Models, Animal
  • Epitopes / immunology
  • Epitopes / pharmacology*
  • Female
  • Gonorrhea / genetics
  • Gonorrhea / immunology
  • Gonorrhea / prevention & control*
  • Humans
  • Immunization, Passive
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neisseria gonorrhoeae / genetics
  • Neisseria gonorrhoeae / immunology*
  • Peptides / immunology
  • Peptides / pharmacology
  • Polysaccharides, Bacterial / immunology
  • Polysaccharides, Bacterial / pharmacology*
  • Th1 Cells / immunology
  • Th1 Cells / pathology


  • Antibodies, Bacterial
  • Antibodies, Monoclonal, Murine-Derived
  • Bacterial Vaccines
  • Epitopes
  • Immunoglobulin G
  • Peptides
  • Polysaccharides, Bacterial