BACKGROUND
Gonorrhea, caused by Neisseria gonorrhoeae (Ng) represents a significant public health threat that could be effectively mitigated by a vaccine. There has been renewed hope that an effective vaccine may be possible resulting from real-world data on meningococcal outer membrane vesicle (OMV)-based vaccines, such as 4CMenB, which have consistently shown moderate effectiveness against gonorrhea. NgG is an investigational Ng vaccine based on Generalized Modules for Membrane Antigens (GMMA) which includes genetically detoxified OMVs from the FA1090 strain which has been tested pre-clinically and in the clinic in a first time in human trial.
AIM/METHODS
Here we review preclinical data produced from immune studies in mice of the NgG vaccine in light of recent clinical data (NCT05630859).
RESULTS
NgG induced a robust immune response in mice and outperformed the comparator vaccine 4CMenB in several serological and functional tests across multiple Ng strains. Murine monoclonal antibodies isolated from mice immunized with NgG and directed to Opacity proteins and lipooligosaccharide resulted to be functional in vitro and protective in a challenge mouse model, hence highlighting potential key antigen components of the vaccine.
We have completed a seamless phase I/II -Proof of Concept study evaluating the safety, immunogenicity and efficacy of the NgG early-stage vaccine candidate in subjects at very high-risk of gonococcal infection. Immunogenicity was assessed by measuring IgG titers to the Ng GMMA component and by measuring bactericidal activity towards the FA1090 strain. The vaccine candidate was shown to be safe but did not meet the pre-defined efficacy and immunologic criteria. The study and its full results will be published in a peer-reviewed journal.
CONCLUSIONS
The NgG vaccine candidate while demonstrating strong preclinical data, failed to prevent gonococcal infection in very high-risk subjects. The immune responses that we have measured from mouse preclinical studies did not anticipate the immunogenicity observed in the clinical trial. With our current lack of correlates of protection and incomplete understanding of the role of pre-existing immunity, our understanding of preclinical immune responses that could predict protection in humans remains challenging.
Funding: GSK