Oral immunization of BALB/c mice with recombinant Helicobacter pylori antigens and double mutant heat-labile toxin (dmLT) induces prophylactic protective immunity against H. pylori infection

Abstract

Helicobacter pylori infection and associated diseases remain a major public health problem worldwide. Much effort has been made over the last several decades in vaccine development, but there is no licensed vaccine on the market. We have previously reported that oral immunization with H. pylori lysates and double mutant heat-labile toxin (dmLT) affords prophylactic protection against H. pylori infection in mice. In the present study, we investigated the effects of oral immunization with recombinant H. pylori protein antigens (NAP/UreA/UreB) and dmLT on H. pylori challenge in BALB/c mice. We found that oral immunization with candidate antigens and dmLT significantly reduced the gastric colonization of H. pylori 6 weeks after challenge, as compared to unimmunized mice. Moreover, the subunit vaccine appeared to provide a better protection than the bacterial lysate vaccine. The immunized mice showed enhanced antigen-specific lymphocyte proliferation, and serum IgG and mucosal IgA responses. Furthermore, the immunization increased the proportion of CD4⁺ IL-17+ lymphocytes in spleen and mesenteric lymph nodes, and enhanced the production of IL-17, IL-16, IL-6 and TNF-α in lymphocyte culture supernatants. Taken together, our results suggest that oral vaccination with recombinant H. pylori antigens (NAP/UreA/UreB) and dmLT confers more effective prophylactic protection against H. pylori infection than whole bacterial lysates in BALB/c mice. The reduction of H. pylori colonization was associated with the induction of antigen-specific Th17 and local mucosal IgA immune responses.

Keywords: BALB/c mice; Helicobacter pylori; Immune responses; Prophylactic vaccine; dmLT.