Immunization against a saccharide epitope accelerates clearance of experimental gonococcal infection

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DOIResolve DOI: http://doi.org/10.1371/journal.ppat.1003559
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TypeArticle
Journal titlePLoS Pathogens
ISSN1553-7366
Volume9
Issue8
Article numbere1003559
Subjectbacterial vaccine; glycosyltransferase; immunoglobulin A; immunoglobulin G; immunoglobulin M; monoclonal antibody 2C7; multi antigenic peptide 1; unclassified drug; article; bacterial clearance; bactericidal activity; colony forming unit; controlled study; enzyme linked immunosorbent assay; female; fractionation; gonorrhea; human; immune response; immunization; mouse; Neisseria gonorrhoeae; nonhuman; passive immunization; polymerase chain reaction; serum bactericidal antibody assay
AbstractThe 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. © 2013 Gulati et al.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); Human Health Therapeutics (HHT-TSH)
Peer reviewedYes
NPARC number21269815
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Record identifier6f8c0c0b-a459-43e1-828d-6a75b235feed
Record created2013-12-13
Record modified2016-05-09
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