Department of Medicine, Division of Infectious Diseases and Immunology; Department of Medicine, Division of Preventive and Behavioral Medicine
Adult; Animals; Antibodies, Bacterial; Antibodies, Monoclonal, Murine-Derived; Bacterial Vaccines; Disease Models, Animal; Epitopes; Female; Gonorrhea; Humans; Immunization, Passive; Immunoglobulin G; Male; Mice; Mice, Inbred BALB C; Neisseria gonorrhoeae; Peptides; Polysaccharides, Bacterial; Th1 Cells
Bacterial Infections and Mycoses | Female Urogenital Diseases and Pregnancy Complications | Immunity | Immunopathology | Immunoprophylaxis and Therapy | Male Urogenital Diseases
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 IgG3lambda 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.
DOI of Published Version
PLoS Pathog. 2013;9(8):e1003559. doi: 10.1371/journal.ppat.1003559. Epub 2013 Aug 29. Link to article on publisher's site
Gulati, Sunita; Zheng, Bo; Reed, George W.; Su, Xiaohong; Cox, Andrew D.; Michael, Frank St.; Stupak, Jacek; Lewis, Lisa A.; Ram, Sanjay; and Rice, Peter A., "Immunization against a saccharide epitope accelerates clearance of experimental gonococcal infection" (2013). University of Massachusetts Medical School Faculty Publications. 449.
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