A novel GMMA-based gonococcal vaccine demonstrates functional immune responses in mice
Marco Spinsanti, Elisabetta Monaci, Giacomo Romagnoli, Giada Buffi, Andrea Guido Oreste Manetti, Filippo Carboni, Giovanna Tuscano, Lucia Eleonora Fontana, Sara Tomei, Marta Zambelli, Rossella Cuffaro, Marianna Taccone, Chiara Sammicheli, Claudia Gianfaldoni, Francesca Angiolini, Maria Giuliani, Sara Marchi, Silvia Senesi, Christian Matano, Ivan Pisoni, Nathalie Norais, Maria Rosaria Romano, Silvia Rossi Paccani, Silvana Savino, Alessandro Muzzi, Federico Fontani, Davide Serruto, Michela Brazzoli, Giulia Giordano, Monica Fabbrini, Ugo D’Oro, Oretta Finco, Immaculada Margarit, Isabel Delany, Erika Bartolini
Abstract
Gonorrhea, caused by Neisseria gonorrhoeae (GC) represents a significant public health threat that may be mitigated by an effective vaccine. Vaccines containing N. meningitidis outer membrane vesicles (OMVs), such as 4CMenB, demonstrated moderate effectiveness in preventing GC infections. Here, we developed NgG, an investigational GC vaccine based on Generalized Modules for Membrane Antigens (GMMA). NgG includes genetically detoxified OMVs from the FA1090 strain, engineered to reduce endotoxin activity and limit immune interference. NgG induced a robust immune response in mice and outperformed the comparator vaccine 4CMenB in several serological and functional tests. Immunization with GMMA from a FA1090 mutant, where major oligosaccharide epitopes are incomplete or absent, revealed that NgG lipooligosaccharide plays a major role in the breadth of functional responses, with protein component also contributing in some GC strains. These results suggest that NgG has the potential to block GC infection through various mechanisms, supporting further vaccine development.