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Histopathological Observation of Immunized Rhesus Macaques with Plague Vaccines after Subcutaneous Infection of Yersinia pestis

By Guang Tian, Yefeng Qiu, Zhizhen Qi, Xiaohong Wu, Qingwen Zhang, Yujing Bi, Yonghai Yang, Yuchuan Li, Xiaoyan Yang, Youquan Xin, Cunxiang Li, Baizhong Cui, Zuyun Wang, Hu Wang, Ruifu Yang and Xiaoyi Wang


In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270) and SV2 (200 µg F1 and 100 µg rV270) subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×106 CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs) of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague

Topics: Research Article
Publisher: Public Library of Science
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Provided by: PubMed Central

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  1. (2001). A Comparison of Routine and Rapid Microwave Tissue Processing in a Surgical Pathology Laboratory.
  2. (1997). A sub-unit vaccine elicits IgG in serum, spleen cell cultures and bronchial washings and protects immunized animals against pneumonic plague.
  3. (1999). An IgG1 titre to the F1 and V antigens correlates with protection against plague in the mouse model. Clin Exp Immunol 116: 107–114. Histopathological Observation of Rhesus Macaques
  4. (2008). Broad T cell immunity to the LcrV virulence protein is induced by targeted delivery to DEC205/CD205-positive mouse dendritic cells.
  5. (2005). Cell-mediated protection against pulmonary Yersinia pestis infection.
  6. (2008). Characterization of a mouse model of plague after aerosolization of Yersinia pestis CO92.
  7. (2008). Clinical and Pathologic Features of Cynomolgus Macaques (Macaca fascicularis) Infected with Aerosolized Yersinia pestis.
  8. (2010). Comparison of mouse, guinea pig and rabbit models for evaluation of plague subunit vaccine F1+rV270.
  9. (2008). Defective innate cell response and lymph node infiltration specify Yersinia pestis infection.
  10. (2007). Development of in vitro correlate assays of immunity to infection with Yersinia pestis.
  11. (2004). Frequent vaccination and immune complex deposition in unilateral nephrectomized mice.
  12. (2001). Histopathology of experimental plague in cats.
  13. (2000). Human plague in
  14. (2008). Immune defense against pneumonic plague.
  15. (2008). Immunization with recombinant V10 protects cynomolgus macaques from lethal pneumonic plague.
  16. (2009). Immunodrugs: Therapeutic VLP-Based Vaccines for Chronic Diseases.
  17. (2009). Immunohistochemical detection and localization of new type gosling viral enteritis virus in paraformaldehyde-fixed paraffin-embedded tissue.
  18. (2005). Kinetics of disease progression and host response in a rat model of bubonic plague.
  19. (1985). Mechanisms of glomerular injury in immune complex disease.
  20. (2009). Modulation of tropoelastin and fibrillin-1 by infrared radiation in human skin in vivo.
  21. (1996). Pathology of experimental pneumonic plague produced by fraction 1-positive and fraction 1-negative Yersinia pestis in African green monkeys (Cercopithecus aethiops).
  22. (2005). Plague: from natural disease to bioterrorism.
  23. (2005). Progression of primary pneumonic plague: a mouse model of infection, pathology, and bacterial transcriptional activity.
  24. (1987). Removal of subepithelial immune complexes with excess unaltered or cationic antigen.
  25. (2006). The use of non-human primates in research. The Academy of Medical Sciences.
  26. (2001). Ultrastructural pathology of nasal and tracheal mucosa of rabbits experimentally infected with Pasteurella multocida serotype D:1.
  27. (1997). Yersinia pestis-etiologic agent of plague.