Immunization against a Saccharide Epitope Accelerates Clearance of Experimental Gonococcal Infection

PLoS Pathogens

Sanjay Ram¹  Peter A. Rice¹  Sunita Gulati¹  Bo Zheng¹  Xiaohong Su¹  George W. Reed²  Andrew D. Cox³  Frank St. Michael⁴  Jacek Stupak⁴  Lisa A. Lewis⁴ 

[1] Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America;Department of Medicine, Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America;Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing, People's Republic of China;Vaccine Program, Human Health Therapeutics Portfolio, National Research Council Canada, Ottawa, Ontario, Canada

关键词: Antibodies;    Neisseria gonorrhoeae;    Mouse models;    Vaccines;    Complement system;    Immune response;    Animal models of infection;    Enzyme-linked immunoassays;   

DOI  :  10.1371/journal.ppat.1003559

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY