<i>Yersinia pestis</i>biovar<i>Microtus</i>strain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques

Zhang, Qingwen; Wang, Qiong; Guang, Tian; Zhang, Qi; Zhang, Xuecan; Wu, Xiaohong; Qiu, Yefeng; Bi, Yujing; Yang, Xiaoyan; Xin, Youquan; He, Jun; Zhou, Jiyuan; Zeng, Lin; Wang, Xiaoyi

doi:10.4161/hv.27060

Cited by 12 publications

(17 citation statements)

References 64 publications

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“…The immunization with Y. pestis Microtus strain 201 induced elevated secretion of both Th1-associated cytokines (IFN-γ, IL-2 and TNF-α) and Th2-associated cytokines (IL-4, IL-5, and IL-6), as well as chemokines MCP-1 and IL-8. However, the protected animals developed skin ulcer at challenge site with different severity in most of the 201-immunized and some of the EV-immunized monkeys [140]. …”

Section: Live Attenuated Yersinia Vaccinesmentioning

confidence: 99%

Plague Vaccines: Status and Future

Sun

2016

Advances in Experimental Medicine and Biology

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Three major plague pandemics caused by the gram-negative bacterium Yersinia pestis have killed nearly 200 million people in human history. Due to its extreme virulence and the ease of its transmission, Y. pestis has been used purposefully for biowarfare in the past. Currently, plague epidemics are still breaking out sporadically in most of parts of the world, including the United States. Approximately 2000 cases of plague are reported each year to the World Health Organization. However, the potential use of the bacteria in modern times as an agent of bioterrorism and the emergence of a Y. pestis strain resistant to eight antibiotics bring out severe public health concerns. Therefore, prophylactic vaccination against this disease holds the brightest prospect for its long-term prevention. Here, we summarize the progress of the current vaccine development for counteracting plague.

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Section: Live Attenuated Yersinia Vaccinesmentioning

confidence: 99%

Plague Vaccines: Status and Future

Sun

2016

Advances in Experimental Medicine and Biology

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“…All the animals survive the infection with the Y. pestis Microtus 201 (1.4 £ 10 10 CFU) or the EV vaccine (1.57 £ 10 10 CFU), and no systemic symptoms were observed in these 2 groups of animals. 10 This result seems to indicate that these 2 strains of Y. pestis had similar virulence by subcutaneous route. To further evaluate the virulence of these 2 strains of Y. pestis, 2 animals were first injected intravenously in a preliminary experiment to predict the virulence of the Y. pestis Microtus 201 and the vaccine EV.…”

Section: Clinical Signs and Post-mortem Observationmentioning

confidence: 74%

“…19 Our recent study showed that another Y. pestis Microtus 201 has a low virulence by the s.c. route in the Chinese-origin rhesus macaque model, and provides a protective efficacy similar to the EV vaccine against bubonic plague by generating strong Th1-type cellular and Th2type humoral immune responses. 10 These results seem to signify that the Y. pestis Microtus 201 or 91001 may be a promising live attenuated plague vaccine candidate. However, although no plague symptom was observed in humans by superficial skin scarification with 5.1 £ 10 6 CFU of the Y. pestis strain 91001, 19 the dose and mode of inoculation were not enough to illustrate this strain to be completely safe for humans.…”

Section: Discussionmentioning

confidence: 96%

“…The Y. pestis Microtus 201 represented a good plague vaccine candidate based on its ability to generate strong cytokine-mediated Th1-type cellular immune response and Th2-type humoral immune response as well as its good protection against high dose of subcutaneous virulent Y. pestis 141 challenge. 10 Recently, a case of lethal septicemic plague caused by an attenuated pgm -m utant of Y. pestis was reported in an U. S. laboratory. In this case, hereditary hemochromatosis caused by a C282Y mutation appears to be the leading cause of death.…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17] Therefore, it is imperative to explore novel rationally attenuated Y. pestis mutants as vaccine candidates for use against plague. Although we have demonstrated that the Y. pestis Microtus 201 strain shows a good plague vaccine candidate, and has a low virulence by the s.c. route in the Chinese-origin rhesus macaque model, 10 its virulence has not been evaluated by the intranasal (i.n.) or intravenous (i.v.)…”

Section: Introductionmentioning

confidence: 99%

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Comparison of virulence between theYersinia pestis Microtus201, an avirulent strain to humans, and the vaccine strain EV in rhesus macaques,Macaca mulatta

Guang

Zhang

Qiu

et al. 2014

Human Vaccines & Immunotherapeutics

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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 10(9) CFU of the Y. pestis Microtus 201, but all the animals succumbed to 10(10) CFU of intravenous infection. By contrast, all the animals survive intravenous infection with 10(10) CFU of the vaccine EV. Post-mortem examination showed multiple areas of severe abscess in the lungs of the dead animals infected with 10(10) 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.

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Pathology and Pathogenesis of Yersinia pestis

Wang

2016

Advances in Experimental Medicine and Biology

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Various types of animal models of plague have been developed, including mice, rats, guinea pigs, and nonhuman primates. Studies have indicated that rodent and nonhuman primate models of pneumonic plague closely resemble the human disease and that the pathologic changes that occur during bubonic plague are very similar in rodents, nonhuman primates, and humans. In this section, the pathological changes caused by Y. pestis in different animal models are described. The bacterium Y. pestis causes deadly plague, whereas the other two closely related enteropathogenic Yersinia species merely cause limited gastrointestinal manifestations. Y. pestis has unique virulence mechanisms that enable it to be a successful flea-borne and highly virulent pathogen. Massive gene losses and inactivation play important roles, as well as the gene acquisitions, in the evolution process of this pathogen. Here, we summarized several newly acquired features of Y. pestis, including the unique lipid A modification, biofilm formation ability, and loss of adhesions for enteric colonization that are realized by gene inactivation and plasminogen activator and F1 capsular that are realized by gene acquisition, which contribute to the unique transmission and pathogenesis of Y. pestis.

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Yersinia pestisbiovarMicrotusstrain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques

Cited by 12 publications

References 64 publications

Plague Vaccines: Status and Future

Plague Vaccines: Status and Future

Comparison of virulence between theYersinia pestis Microtus201, an avirulent strain to humans, and the vaccine strain EV in rhesus macaques,Macaca mulatta

Pathology and Pathogenesis of Yersinia pestis

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