The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae.
Animals
Antigens, Bacterial
/ immunology
Bacterial Outer Membrane Proteins
/ immunology
Bacterial Vaccines
/ immunology
Case-Control Studies
Cross Protection
/ immunology
Cross Reactions
/ immunology
Female
Gonorrhea
/ immunology
Humans
Immune Sera
/ immunology
Immunization
/ methods
Male
Meningococcal Infections
/ microbiology
Meningococcal Vaccines
/ immunology
Mice
Mice, Inbred BALB C
Neisseria gonorrhoeae
/ immunology
Neisseria meningitidis
/ immunology
Neisseria meningitidis, Serogroup B
/ immunology
Retrospective Studies
Serogroup
Vaccination
/ methods
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
30
04
2020
accepted:
08
10
2020
revised:
18
12
2020
pubmed:
9
12
2020
medline:
30
1
2021
entrez:
8
12
2020
Statut:
epublish
Résumé
There is a pressing need for a gonorrhea vaccine due to the high disease burden associated with gonococcal infections globally and the rapid evolution of antibiotic resistance in Neisseria gonorrhoeae (Ng). Current gonorrhea vaccine research is in the stages of antigen discovery and the identification of protective immune responses, and no vaccine has been tested in clinical trials in over 30 years. Recently, however, it was reported in a retrospective case-control study that vaccination of humans with a serogroup B Neisseria meningitidis (Nm) outer membrane vesicle (OMV) vaccine (MeNZB) was associated with reduced rates of gonorrhea. Here we directly tested the hypothesis that Nm OMVs induce cross-protection against gonorrhea in a well-characterized female mouse model of Ng genital tract infection. We found that immunization with the licensed Nm OMV-based vaccine 4CMenB (Bexsero) significantly accelerated clearance and reduced the Ng bacterial burden compared to administration of alum or PBS. Serum IgG and vaginal IgA and IgG that cross-reacted with Ng OMVs were induced by 4CMenB vaccination by either the subcutaneous or intraperitoneal routes. Antibodies from vaccinated mice recognized several Ng surface proteins, including PilQ, BamA, MtrE, NHBA (known to be recognized by humans), PorB, and Opa. Immune sera from both mice and humans recognized Ng PilQ and several proteins of similar apparent molecular weight, but MtrE was only recognized by mouse serum. Pooled sera from 4CMenB-immunized mice showed a 4-fold increase in serum bactericidal50 titers against the challenge strain; in contrast, no significant difference in bactericidal activity was detected when sera from 4CMenB-immunized and unimmunized subjects were compared. Our findings directly support epidemiological evidence that Nm OMVs confer cross-species protection against gonorrhea, and implicate several Ng surface antigens as potentially protective targets. Additionally, this study further defines the usefulness of murine infection model as a relevant experimental system for gonorrhea vaccine development.
Identifiants
pubmed: 33290434
doi: 10.1371/journal.ppat.1008602
pii: PPATHOGENS-D-20-00890
pmc: PMC7748408
doi:
Substances chimiques
4CMenB vaccine
0
Antigens, Bacterial
0
Bacterial Outer Membrane Proteins
0
Bacterial Vaccines
0
Immune Sera
0
Meningococcal Vaccines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008602Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007273
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI144180
Pays : United States
Organisme : NIAID NIH HHS
ID : UC6 AI058607
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing financial interests exist.
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