Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
Vaccine. 2011 Sep 2;29(38):6572-83. doi: 10.1016/j.vaccine.2011.06.119. Epub 2011 Jul 16.
Yersinia pestis causes plague, a disease with high mortality in humans that can be transmitted by fleabite or aerosol. A US Food and Drug Administration (FDA)-licensed plague vaccine is currently not available. Vaccine developers have focused on two subunits of Y. pestis: LcrV, a protein at the tip of type III secretion needles, and F1, the fraction 1 pilus antigen. F1-V, a hybrid generated via translational fusion of both antigens, is being developed for licensure as a plague vaccine. The rV10 vaccine is a non-toxigenic variant of LcrV lacking residues 271-300. Here we developed Current Good Manufacturing Practice (cGMP) protocols for rV10. Comparison of clinical grade rV10 with F1-V did not reveal significant differences in plague protection in mice, guinea pigs or cynomolgus macaques. We also developed cGMP protocols for rV10-2, a variant of rV10 with an altered affinity tag. Immunization with rV10-2 adsorbed to aluminum hydroxide elicited antibodies against LcrV and conferred pneumonic plague protection in mice, rats, guinea pigs, cynomolgus macaques and African Green monkeys. The data support further development of rV10-2 for FDA Investigational New Drug (IND) authorization review and clinical testing.
鼠疫耶尔森菌引起鼠疫，这是一种人类死亡率很高的疾病，可以通过跳蚤叮咬或气溶胶传播。目前，美国食品和药物管理局 (FDA) 批准的鼠疫疫苗尚未上市。疫苗开发商专注于鼠疫耶尔森菌的两个亚单位：LcrV，一种位于 III 型分泌针尖端的蛋白质，以及 F1，即分 1 菌毛抗原。F1-V 是通过两种抗原的翻译融合产生的杂交体，正在开发中以获得鼠疫疫苗的许可。rV10 疫苗是一种缺乏残基 271-300 的无毒力 LcrV 变体。在这里，我们开发了 rV10 的现行良好生产规范 (cGMP) 协议。临床级 rV10 与 F1-V 的比较并未显示在小鼠、豚鼠或食蟹猴中鼠疫保护方面有显着差异。我们还开发了 rV10-2 的 cGMP 协议，rV10-2 是一种具有改变的亲和标签的 rV10 变体。用吸附在氢氧化铝上的 rV10-2 免疫可诱导针对 LcrV 的抗体，并可在小鼠、大鼠、豚鼠、食蟹猴和非洲绿猴中提供肺鼠疫保护。这些数据支持进一步开发 rV10-2 以获得 FDA 新药研究 (IND) 授权审查和临床测试。
