Unité de Recherche Yersinia, Institut Pasteur, Paris, France.
PLoS Negl Trop Dis. 2012;6(2):e1528. doi: 10.1371/journal.pntd.0001528. Epub 2012 Feb 14.
Plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined.
The sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells) and the mucosal levels (IgA and Th17 cells). A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD(50) of the fully virulent Y. pestis CO92 strain) and 94% against a high challenge dose (3,300×LD(50)). Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis.
The encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality.
plague 仍然是世界公共卫生问题，并且正在重新出现，但尚无有效的疫苗。我们之前报道过，口服接种减毒活的yersinia pseudotuberculosis（鼠疫耶尔森菌的近期祖先）可提供抗鼠疫的保护。然而，该菌株对肺鼠疫的保护作用较差，肺鼠疫是该病最致命和最具传染性的形式，并且其遗传特性尚未明确。
经过基因缺失三个必需毒力因子，测序的yersinia pseudotuberculosis IP32953 已不可逆地减毒。通过克隆鼠疫耶尔森菌 F1 编码 caf 操纵子并在减毒菌株中表达，生成了荚膜型yersinia pseudotuberculosis。新的 V674pF1 菌株在体外和体内产生 F1 荚膜。口服接种 V674pF1 后，可在肠道定植，而不会导致派尔集合淋巴结和脾脏发生病变。接种可诱导全身（IgG 和 Th1 细胞）和黏膜水平（IgA 和 Th17 细胞）的体液和细胞免疫成分。单次口服剂量可提供针对致死性肺鼠疫挑战（完全毒力鼠疫耶尔森菌 CO92 株的 33×LD50）的 100%保护，对高挑战剂量（3300×LD50）的保护率为 94%。F1 和其他耶尔森氏菌抗原均被识别，并且 V674pF1 可有效保护免受 F1 阴性鼠疫耶尔森菌的侵害。
荚膜型yersinia pseudotuberculosis V674pF1 是一种针对肺鼠疫的有效口服活疫苗，可在热带流行地区大规模接种，以控制肺鼠疫的传播和死亡率。
