Sterilizing immunity against experimental Helicobacter pylori infection ischallenge-strain dependent

The development of a murine model of Helicobacter pylori infection through serial in vivo passage of candidate strains has enabled a quantitative asse ssment of vaccine efficacy. In this study we compare infection with and pro tection against challenge from both CagA(+) type I, and CagA(-) type II in vivo adapted isolates. In vivo passage of a type II H. pylori isolate resul ted in a highly infectious strain (X47-2AL), capable of reproducibly infect ing mice to high density (10(7) CFU/g of gastric tissue). Similarly adapted type I strains were found to colonize mice at a significantly lower level (10(4)-10(5) CFU/g tissue). Mucosal immunization with recombinant urease (r Ure) significantly protected animals against both types. Protection against X47-2AL was characterized by a greater than or equal to 100-fold (or 2 log ) reduction in bacterial density. However, the presence of a residual infec tion highlighted the inability to achieve sterilizing immunity against this strain. The level of protection appeared independent of challenge dose, an d was stable for up to 6 months, all animals exhibiting a low-level residua l infection that did not recrudesce with time. Similarly immunized mice cha llenged with isolates representing the residual infection were also protect ed, confirming that they did not represent a sub-population of H. pylori th at could escape immunity. Immunization and challenge studies with type I ad apted-isolates, demonstrated a similar 2-3 log reduction in the bacterial b urden, but that in this instance resulted in sterilizing immunity. These re sults suggest varied specificity for the murine host by different Helicobac ter strains that can influence the outcome of both infection and immunity. (C) 2001 Elsevier Science Ltd. All rights reserved.