Mucosal vaccination with enzymatically active Helicobacter pylori γ-glutamyl transferase (GGT) adjuvanted with STING-agonist elicits robust Th1/Th17 immunity in mice.

Helicobacter pylori infection is the leading cause of chronic gastritis and a major risk factor for gastric cancer, yet no licensed vaccine is currently available. The H. pylori γ-glutamyl transferase (hpGGT) is a key virulence factor that contributes to bacterial colonization and persistence, making it a promising antigen for vaccine development. Although hpGGT has been reported to exert immunosuppressive effects through its enzymatic activity, whether the enzymatic activity affects its immunogenicity is unknown. To address this question, we intranasally immunized mice with recombinant wild-type hpGGT (WT-GGT) or a structurally similar, enzymatically inactive variant (In-GGT), each formulated with a liposomal STING-agonist adjuvant. Despite the potential for immunosuppression, the enzymatically active WT-GGT was the superior immunogen: it elicited robust Th1 and Th17 responses, along with strong gastric IgA production-immune features known to be critical for protection against H. pylori. These findings demonstrate that intranasal immunization with WT-GGT combined with a STING-agonist adjuvant induces mucosal and cellular immunity, supporting its potential as a viable vaccine strategy against H. pylori.