Mycobacterium ulcerans Mouse Model Refinement for Pre-Clinical Profiling of Vaccine Candidates

Buruli Ulcer is a neglected tropical disease leading to extensive disabilities and morbidity in West Africa. In this paper we sought to characterize various strains of Mycobacterium ulcerans (M.ulcerans) with different origins and laboratory passage records while refining a mouse model for Buruli ulcer. We described, compared and followed the kinetics of the histo-pathological outcome of infection of a collection of strains at various anatomical sites of infection in order to find a suitable model for further immunization studies. Moreover we compared the outcome of infection in C57Bl/6 and Balbc/J mice. Specifically we described thoroughly one M. ulcerans strain characterized by slow growth rate and limited tissue necrosis, which presents close ressemblance with the infection kinetics in humans. This strain caused macrophages as well as T and B cells infiltration, correlating with mycobacterial proliferation at the site of infection as well as in the draining lymph nodes, making it a suitable strain to screen vaccine candidates efficacy.

布鲁里溃疡（Buruli Ulcer）是一类被忽视的热带病，在西非地区可引发广泛残疾与高发病负担。本研究旨在对不同来源及实验室传代记录各异的溃疡分枝杆菌（Mycobacterium ulcerans，M. ulcerans）各菌株进行表征，并同步优化布鲁里溃疡的小鼠感染模型。我们对一系列菌株在不同感染解剖部位的感染组织病理学动力学变化进行了描述、比较与追踪，以期筛选出适用于后续免疫研究的理想动物模型。此外，我们还比较了C57Bl/6与Balbc/J两种小鼠品系的感染结局。具体而言，我们详细表征了一株生长缓慢、组织坏死程度有限的溃疡分枝杆菌菌株，该菌株的感染动力学特征与人类感染情况高度相似。该菌株可诱导巨噬细胞、T细胞及B细胞发生浸润，且该浸润情况与感染部位及引流淋巴结内的分枝杆菌增殖水平呈正相关，因此可作为筛选疫苗候选物有效性的理想菌株。