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首页> 外文期刊>Vaccine >Sterilizing immunity against experimental Helicobacter pylori infection ischallenge-strain dependent
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Sterilizing immunity against experimental Helicobacter pylori infection ischallenge-strain dependent

机译：针对实验性幽门螺杆菌感染的无菌免疫挑战株

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摘要

The development of a murine model of Helicobacter pylori infection through serial in vivo passage of candidate strains has enabled a quantitative assessment of vaccine efficacy. In this study we compare infection with and protection 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 resulted in a highly infectious strain (X47-2AL), capable of reproducibly infecting 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 (rUre) 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 infection highlighted the inability to achieve sterilizing immunity against this strain. The level of protection appeared independent of challenge dose, and was stable for up to 6 months, all animals exhibiting a low-level residual infection that did not recrudesce with time. Similarly immunized mice challenged with isolates representing the residual infection were also protected, confirming that they did not represent a sub-population of H. pylori that could escape immunity. Immunization and challenge studies with type I adapted-isolates, demonstrated a similar 2-3 log reduction in the bacterial burden, but that in this instance resulted in sterilizing immunity. These results suggest varied specificity for the murine host by different Helicobacter strains that can influence the outcome of both infection and immunity.
机译：通过候选菌株的体内连续传代产生幽门螺杆菌感染的鼠模型，可以定量评估疫苗效力。在这项研究中，我们比较了在体内适应的分离株中，I型CagA（+）和II型CagA（-）的感染情况和针对其的攻击防护。 II型幽门螺杆菌分离株的体内传代产生了高度感染性的菌株（X47-2AL），能够以高密度（10（7）CFU / g胃组织）感染小鼠。发现类似适应的I型毒株以明显较低的水平（10（4）-10（5）CFU / g组织）定居小鼠。用重组脲酶（rUre）进行粘膜免疫可显着保护动物免受两种类型的侵害。针对X47-2AL的防护的特征是细菌密度降低了大于或等于100倍（或2 log）。但是，残留感染的存在突出表明无法获得针对该菌株的灭菌免疫力。保护水平似乎与攻击剂量无关，并且可以稳定长达6个月，所有动物均表现出低水平的残留感染，并且不会随时间推移而复发。同样，用代表残留感染的分离株攻击的免疫小鼠也得到了保护，证实它们不代表可以逃避免疫的幽门螺杆菌亚群。用I型适应分离株进行的免疫和攻毒研究表明，细菌负担减少了2-3 log，但在这种情况下导致了对免疫的杀菌。这些结果表明，不同的幽门螺杆菌菌株对鼠宿主的特异性不同，可以影响感染和免疫的结果。

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