Parenteral immunization with a cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) adjuvanted <i>Helicobacter pylori</i> vaccine induces protective immunity against <i>H. pylori</i> infection in mice

Abstract

Under the trend of antibiotic resistance of <i>H. pylori</i> leading to the decrease of eradication rate, the development of a vaccine is the best choice to fight against <i>H. pylori</i>. In this study, we attempted to reduce the amounts of required antigens by using three different parenteral routes of immunization and an adjuvant cGAMP (cyclic guanosine monophosphate-adenosine monophosphate) to enhance the immunogenicity of the vaccine candidate. The immune protection and post-challenge immune responses were assessed and compared in mice immunized with recombinant <i>Helicobacter pylori</i> urease A, urease B, and neutrophil-activating protein adjuvanted with cGAMP. The gastric mucosal colonization by <i>H. pylori</i> was significantly reduced in mice immunized by intranasal and, to a less degree, subcutaneous route, but not by intramuscular route. All immunized mice, regardless of the route of immunization, displayed significant, but comparable, increases in antigen-specific serum IgG and mucosal IgA responses 5 weeks post-challenge. The magnitude of the vaccine-induced protection appeared to be associated with the level of antigen-specific Th1 and particularly Th17 responses, as IL-17 responses were only detected in intranasally immunized mice. Taken together, we explored and confirmed the possibility of using a novel adjuvant (cGAMP) to induce significant protective immunity with 10% of oral vaccine antigen dosage through parenteral immunization, especially intranasal immunization. This may provide an alternative approach to oral immunization for the development of effective <i>H. pylori</i> vaccines.