| DOI | Trouver le DOI : https://doi.org/10.1371/journal.ppat.1003559 |
|---|
| Auteur | Rechercher : Gulati, S.; Rechercher : Zheng, B.; Rechercher : Reed, G.W.; Rechercher : Su, X.; Rechercher : Cox, A.D.1; Rechercher : St. Michael, F.1; Rechercher : Stupak, J.1; Rechercher : Lewis, L.A.; Rechercher : Ram, S.; Rechercher : Rice, P.A. |
|---|
| Affiliation | - Conseil national de recherches du Canada. Thérapeutique en santé humaine
|
|---|
| Format | Texte, Article |
|---|
| Sujet | bacterial vaccine; glycosyltransferase; immunoglobulin A; immunoglobulin G; immunoglobulin M; monoclonal antibody 2C7; multi antigenic peptide 1; unclassified drug; bacterial clearance; bactericidal activity; colony forming unit; enzyme linked immunosorbent assay; female; fractionation; gonorrhea; immune response; immunization; mouse; Neisseria gonorrhoeae; passive immunization; polymerase chain reaction; serum bactericidal antibody assay |
|---|
| Résumé | 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. © 2013 Gulati et al. |
|---|
| Date de publication | 2013 |
|---|
| Dans | |
|---|
| Langue | anglais |
|---|
| Publications évaluées par des pairs | Oui |
|---|
| Numéro NPARC | 21269815 |
|---|
| Exporter la notice | Exporter en format RIS |
|---|
| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
|---|
| Identificateur de l’enregistrement | 6f8c0c0b-a459-43e1-828d-6a75b235feed |
|---|
| Enregistrement créé | 2013-12-13 |
|---|
| Enregistrement modifié | 2021-09-17 |
|---|
