Advancing a native outer membrane vesicle vaccine against gonorrhoea towards clinical development

Professor Calman MacLennan, MRC Senior Clinical Fellow
Jenner Investigator and Group Leader
Jenner Institute, University of Oxford (UK)

Cal MacLennan

Collaborators:
Professor Sanjay Ram, University of Massachusetts Medical School (USA)
Dr Paula Freixeiro, Jenner Institute, University of Oxford (UK)
Dr Christine Rollier, Oxford Vaccine Group, University of Oxford (UK)
Dr Robert W. Kaminski, Walter Reed Army Institute of Research (WRAIR) (USA)
Dr Sinead Delany-Moretlwe, University of the Witwatersrand (South Africa)

SUMMARY
Gonorrhoea, a sexual transmitted infection, is a global problem disproportionately affecting women and infants in LMICs. Complications include pelvic inflammatory disease, ectopic pregnancy, infertility and infant blindness. The problem is exacerbated by increasing resistance to antibiotics which threatens to make gonorrhoea untreatable. There is no licensed gonococcal vaccine. However, a retrospective study of the MenZB meningococcal outer membrane vesicle (OMV) vaccine in New Zealand estimated 31% effectiveness against gonorrhoea. Gonococcus is closely related to meningococcus. We hypothesise that OMV produced from gonococcus instead of meningococcus will better protect against gonorrhoea than MenZB. We have genetically modified a circulating gonococcal strain to produce a gonococcal OMV-based candidate vaccine. This can induce an immune response in mice. We need to understand whether this or a similar candidate OMV vaccine can confer protection.

To test our hypothesis, we will evaluate gonococcal OMVs in the mouse gonorrhoea model. To maximise our chance of success, we will engineer a meningococcal and second gonococcal strain to produce two further OMV vaccine candidates replicating our vaccine design. All three OMV vaccines will be characterised and tested in the mouse gonorrhoea model compared with Bexsero, the commercial four-component meningococcal vaccine which contains MenZB OMVs. If one of our OMV candidate vaccines accelerates clearance of gonococcal infection in mice, this will support advancing the vaccine into clinical development and testing in humans. Finally, we will explore the immunological mechanisms behind the action of the OMV candidates, to help identify correlates of protection that will be valuable for clinical development.