Comparison of virulence between the Yersinia pestis Microtus 201, an avirulent strain to humans, and the vaccine strain EV in rhesus macaques, Macaca mulatta

Our previous study has demonstrated that Yersinia pestis Microtus 201 is a low virulent strain to the Chinese- origin rhesus macaques, Macaca mulatta, and can protect it against high dose of virulent Y. pestis challenge by subcutaneous route. To investigate whether the Y. pestis Microtus 201 can be used as a live attenuated vaccine candidate, in this study its intravenous virulence was determined and compared with the live attenuated vaccine strain EV in the Chinese- origin rhesus macaque model. The results showed that the Chinese- origin rhesus macaques can survive intravenous infection with approximately 109 CFU of the Y. pestis Microtus 201, but all the animals succumbed to 1010 CFU of intravenous infection. By contrast, all the animals survive intravenous infection with 1010 CFU of the vaccine EV. Post- mortem examination showed multiple areas of severe abscess in the lungs of the dead animals infected with 1010 CFU of the Y. pestis Microtus 201, whereas histopathology observation, microbiological examination and immunohistochemistry staining showed that the Y. pestis Microtus 201 also invaded hearts, livers, spleens, kidneys and lymph nodes and caused different degrees of pathological changes in these organs. These results indicated that the Y. pestis Microtus 201 is indeed low virulent to monkeys, but it is more virulent than the vaccine EV when administered by intravenous route. The Y. pestis Microtus 201 mainly attack the lungs when administered by intravenous infection, which may be the leading cause of animal death.