Abstract
The current vaccine development for Helicobacter pylori (H. pylori) still faces challenges of weak immune responses stimulated by existing antigens and a lack of safe adjuvants. The modification of the lipopolysaccharide (LPS) structure by H. pylori is an important mechanism involved in its immune escape. In this study, we developed a novel recombinant vaccine candidate against H. pylori infection by knocking down the key genes (lpxE, lpxF and futB) of LPS modification and employing the bacterial outer membrane vesicles (OMVs) as a vector for delivering UreB, VacA and CagA antigens, and then evaluated its safety and immune protective efficacy in vitro and in vivo mouse model. We measured the antibody and cytokine productions, detected the subtypes of immune cells, and examined the histopathological changes in mice from the control and various experimental groups. We revealed that this OMV-based recombinant vaccine candidate could induce specific humoral immune responses and a Th1/Th2/Th17 mixed immune response, with Th17 being predominant, and markedly protect the mice from H. pylori infection. Our findings suggest that the OMVs with the genetically engineered LPS may function as a vector for delivering recombinant antigens and safe adjuvants for the development of novel vaccine candidates against H. pylori infection.