Protection against Helicobacter pylori infection in mongolian gerbil by intragastric or intramuscular administration of H. pylori multicomponent vaccine.

ABSTRACT

BACKGROUND: Development of Helicobacter pylori vaccine would be a new effective strategy for prevention and treatment of H. pylori infection. Recombinant H. pylori vaccine comprising a single subunit antigen can only induce immune response with limited protection efficiency. In this study, the protective effect of H. pylori multicomponent vaccines consisting of three recombinant subunit antigens was investigated using the Mongolian gerbil model. MATERIALS AND METHODS: Mongolian gerbils were immunized with different formulations of three recombinant H. pylori antigens (UreB, HspA, and HpaA) with two different adjuvants (Al(OH)3, LT(R72DITH)) by intragastric (i.g.) or intramuscular (i.m.) routes. The protective effects of multicomponent vaccines were assessed after H. pylori challenge in different studies. The specific IgG antibodies in serum were monitored by ELISA, and the mRNA expressions of IL-4 and IFN-gamma in spleen tissue were detected by reverse transcribed polymerase chain reaction (RT-PCR). RESULTS: The protective effect against H. pylori challenge in gerbils immunized with three recombinant antigens and LT(R72DITH) or Al(OH)3 was significantly higher than that in single- or double-antigen vaccine-immunized and control gerbils. Furthermore, the protective effect of the triple-antigen vaccine combined with the LT(R72DITH) adjuvant (average 86.3%) was significantly greater than that of vaccine combined with the Al(OH)3 adjuvant (average 53.4%). After the first immunization, the anti-UreB/HspA/HpaA serum IgG level in gerbils immunized with triple-antigen vaccine combined with Al(OH)3 was higher than that in gerbils immunized with the vaccine combined with LT(R72DITH). Splenic interferon (IFN)-gamma and interleukin (IL)-4 transcript levels were significantly increased in LT(R72DITH) vaccine-immunized gerbils as compared to the Al(OH)3 vaccine group. Moreover, splenic IL-4 mRNA levels were higher than IFN-gamma in gerbils immunized with triple-antigen vaccine with either LT(R72DITH) or Al(OH)3. CONCLUSIONS: This study indicated that the recombinant multicomponent vaccine provided effective protection against H. pylori infection as compared to the single-antigen vaccine. This protective immunity would be closely associated with a predominant Th2-type response.