Raghavan S, Hjulström M, Holmgren J, Svennerholm A-M
Department of Medical Microbiology and Immunology and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, S 41346 Göteborg, Sweden.
Infect Immun. 2002 Nov;70(11):6383-8. doi: 10.1128/IAI.70.11.6383-6388.2002.
The protective effect of therapeutic oral immunization with homologous and heterologous formalin-inactivated Helicobacter pylori cells given together with cholera toxin as an adjuvant was evaluated with C57BL/6 mice infected with H. pylori Sydney strain 1 (SS1). The bacteria used for immunization were strains that were either homologous or heterologous with regard to the O antigen (i.e., the Lewis antigen [Le antigen]) expressed by the lipopolysaccharide of the infecting H. pylori SS1 strain. We found that repeated oral immunization with inactivated H. pylori SS1 cells can significantly inhibit an existing infection (P < 0.001) and that the protection induced by such therapeutic immunization extends to protection against reinfection (P < 0.001). A similar level of protection was also achieved by immunization with another inactivated H. pylori strain having the same O antigen (Le antigen) as the infecting H. pylori SS1 strain. In contrast, immunization with inactivated strains expressing a heterologous O antigen, Le(x), provided less protection or no protection. Immunization with H. pylori lysate preparations, on the other hand, resulted in significant comparable protection whether the lysates were prepared from an Le(x) strain or an Le(y) strain. Postimmunization gastritis was seen in mice that were protected after vaccination but not in unimmunized or unprotected mice. In conclusion, therapeutic immunization with inactivated H. pylori whole-cell vaccines may provide strong protection both against experimental H. pylori infection and against later reinfection.
用C57BL/6小鼠感染幽门螺杆菌悉尼菌株1（SS1），评估了以霍乱毒素作为佐剂，口服同源和异源福尔马林灭活幽门螺杆菌细胞进行治疗性免疫的保护作用。用于免疫的细菌菌株在O抗原（即感染的幽门螺杆菌SS1菌株脂多糖所表达的Lewis抗原[Le抗原]）方面，与感染菌株要么同源，要么异源。我们发现，用灭活的幽门螺杆菌SS1细胞进行重复口服免疫可显著抑制现有的感染（P<0.001），并且这种治疗性免疫诱导的保护作用可扩展至预防再感染（P<0.001）。用另一种与感染的幽门螺杆菌SS1菌株具有相同O抗原（Le抗原）的灭活幽门螺杆菌菌株进行免疫，也能达到类似的保护水平。相比之下，用表达异源O抗原Le(x)的灭活菌株进行免疫，提供的保护较少或没有保护作用。另一方面，无论裂解物是由Le(x)菌株还是Le(y)菌株制备的，用幽门螺杆菌裂解物制剂进行免疫都能产生显著相当的保护作用。免疫后胃炎在接种疫苗后得到保护的小鼠中可见，但在未免疫或未得到保护的小鼠中未见。总之，用灭活的幽门螺杆菌全细胞疫苗进行治疗性免疫，可能对实验性幽门螺杆菌感染和随后的再感染都提供强大的保护作用。
