The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae
Abstract
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 inNeisseria 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 BNeisseria meningitidis(Nm) outer membrane vesicle (OMV) vaccine (MeNZB) was associated with reduced rates of gonorrhea. Here we directly tested the hypothesis thatNmOMVs induce cross-protection against gonorrhea in a well-characterized female mouse model ofNggenital tract infection. We found that immunization with the licensedNmOMV-based vaccine 4CMenB (Bexsero) significantly accelerated clearance and reduced theNgbacterial burden compared to administration of alum or PBS. Serum IgG and vaginal IgA and IgG that cross-reacted withNgOMVs were induced by 4CMenB vaccination by either the subcutaneous or intraperitoneal routes. Antibodies from vaccinated mice recognized severalNgsurface proteins, including PilQ, BamA, MtrE, NHBA (known to be recognized by humans), PorB, and Opa. Immune sera from both mice and humans recognizedNgPilQ 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 bactericidal50titers 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 thatNmOMVs confer cross-species protection against gonorrhea, and implicate severalNgsurface 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 08, 2020
- Source ID
- 10.1371/journal.ppat.1008602
Entities
People
- Afrin Begum
- Andrew N. Macintyre
- Ann E. Jerse
- Eric C Garges
- Gregory D Sempowski
- Isabelle Leduc
- Jacqueline T Balthazar
- Joseph A Duncan
- Knashka Underwood
- Kristie L Connolly
- Marguerite B Little
- Nazia Rahman
- Stephen Darnell
- William M Shafer
Organizations
- Defense Health Agency
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- United States Department of Veterans Affairs