Plague in Guinea pigs and its prevention by subunit vaccines.
Plague in Guinea pigs and its prevention by subunit vaccines.
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豚鼠鼠疫及其亚单位疫苗的预防。
DOI：
10.1016/j.ajpath.2010.12.028
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Schneewind,Olaf
中科院分区：
文献类型：
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作者：
Quenee,LaurianeE;Ciletti,Nancy;Berube,Bryan;Krausz,Thomas;Elli,Derek;Hermanas,Timothy;Schneewind,Olaf
人类肺鼠疫是一种破坏性和传播性疾病，目前还没有食品和药物管理局批准的疫苗。可以采用合适的动物模型作为人类鼠疫的替代品，以满足疫苗效力测试的法规要求。为了开发一种非人类灵长类动物肺炎鼠疫的替代品，我们探索了豚鼠作为模型系统。在鼻腔注射完全毒力的鼠疫耶尔森氏菌CO92菌株后，豚鼠出现了致命的肺部感染，并伴有出血性坏死，呼吸系统出现大量细菌复制，血液传播到其他器官系统。鼠疫F1胶囊的表达对于肺部感染的发生并不是必需的；然而，该胶囊似乎对建立腺鼠疫很重要。豚鼠肺鼠疫的平均致死剂量(MLD)估计为1000个集落形成单位。用重组形式的LcrV免疫豚鼠，LcrV是一种位于耶尔森氏菌III型分泌针顶端的蛋白质，或F1胶囊，产生了强大的体液免疫反应。LcrV免疫对250MLD鼠疫菌CO92攻击有部分保护作用，而重组F1免疫则无此作用。RV10是一种缺少LcrV残基271-300的疫苗变体，它对肺炎鼠疫具有保护作用，这似乎是基于针对LcrV的构象抗体。
Human pneumonic plague is a devastating and transmissible disease for which a Food and Drug Administration–approved vaccine is not available. Suitable animal models may be adopted as a surrogate for human plague to fulfill regulatory requirements for vaccine efficacy testing. To develop an alternative to pneumonic plague in nonhuman primates, we explored guinea pigs as a model system. On intranasal instillation of a fully virulent strain, Yersinia pestis CO92, guinea pigs developed lethal lung infections with hemorrhagic necrosis, massive bacterial replication in the respiratory system, and blood-borne dissemination to other organ systems. Expression of the Y. pestis F1 capsule was not required for the development of pulmonary infection; however, the capsule seemed to be important for the establishment of bubonic plague. The mean lethal dose (MLD) for pneumonic plague in guinea pigs was estimated to be 1000 colony-forming units. Immunization of guinea pigs with the recombinant forms of LcrV, a protein that resides at the tip of Yersinia type III secretion needles, or F1 capsule generated robust humoral immune responses. Whereas LcrV immunization resulted in partial protection against pneumonic plague challenge with 250 MLD Y. pestis CO92, immunization with recombinant F1 did not. rV10, a vaccine variant lacking LcrV residues 271-300, elicited protection against pneumonic plague, which seemed to be based on conformational antibodies directed against LcrV.