title: Histopathological observation of immunized rhesus macaques with plague vaccines after subcutaneous infection of Yersinia pestis.
abstract: 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 6×10(6) 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.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Tian
authors.forename: Yefeng
authors.initials: Y
authors.lastname: Qiu
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Qi
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wu
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yujing
authors.initials: Y
authors.lastname: Bi
authors.forename: Yonghai
authors.initials: Y
authors.lastname: Yang
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.forename: Youquan
authors.initials: Y
authors.lastname: Xin
authors.forename: Cunxiang
authors.initials: C
authors.lastname: Li
authors.forename: Baizhong
authors.initials: B
authors.lastname: Cui
authors.forename: Zuyun
authors.initials: Z
authors.lastname: Wang
authors.forename: Hu
authors.initials: H
authors.lastname: Wang
authors.forename: Ruifu
authors.initials: R
authors.lastname: Yang
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001485:Basement Membrane / Q000378:metabolism; D005260:Female; D007114:Immunization; D007150:Immunohistochemistry / Q000379:methods; D007279:Injections, Subcutaneous; D008253:Macaca mulatta / Q000276:immunology*; D008297:Male; D008854:Microscopy, Electron; D010931:Plague Vaccine / Q000276:immunology*; D013234:Stem Cells; D014018:Tissue Distribution; D022223:Vaccines, Subunit / Q000276:immunology; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D010931:Plague Vaccine; D022223:Vaccines, Subunit