PROMOTION OF ULCERATIVE DUODENITIS IN YOUNG FERRETS BY ORAL IMMUNIZATION WITH HELICOBACTER-MUSTELAE AND MURAMYL DIPEPTIDE

Background. The purpose of this study was to determine whether oral im munization of ferret kits with a whole-cell sonicate of Helicobacter m ustelae lysate (Hml) and the adjuvant muramyl dipeptide (MDP) would re duce the incidence of natural colonization with H. mustelae and the ex tent of Helicobacter-associated gastritis by enhancing the host mucosa l immune response. Materials and Methods. Between the ages of 4 and 11 weeks, 44 ferret kits were gavaged with Hml and various doses of MDP. The extent of gastritis and duodenitis and the immune response to H. mustelae were evaluated. Results. All kits became colonized naturally with H. mustelae and the majority developed mild to severe gastritis a nd duodenitis. Kits that received Hml with MDP developed significantly greater inflammation of the gastric antrum and duodenum, as compared to kits vaccinated with Hml alone. Vaccination with Hml and 50 mu g of MDP was associated with severe lesions in the proximal duodenum chara cterized by accumulation of mononuclear inflammatory cells, mucosal er osion, and ulceration. Although serum antibody specific for H. mustela e in 4-week-old kits was approximately 50% of adult levels, a finding attributable to passively acquired maternal antibody, both systemic an d mucosal antibody levels became depressed over time despite oral vacc ination. The humoral immune response was sufficiently low to prevent d etection of any significant dose effect of MDP on antibody levels amon g experimental groups. Conclusions. Oral vaccination of young ferrets with Hml and 50 mu g MDP increased the risk of Helicobacter-associated mucosal ulceration in the proximal duodenum, which was associated wit h low humoral (but significant cell-mediated) immune responses to H. m ustelae. In retrospect, the frequency of vaccination may have suppress ed the systemic humoral immune response, thereby promoting mucosal dam age by H. mustelae. The 50-mu g dose of MDP enhanced the cell-mediated immune response, which indirectly contributed to development of sever e lesions. The increased frequency of mucosal damage associated with t his vaccination regimen enhances the value of the ferret model for stu dying duodenal ulceration secondary to Helicobacter infection.