Leary S E, Griffin K F, Galyov E E, Hewer J, Williamson E D, Holmström A, Forsberg A, Titball R W
Biomedical Sciences Department, Defence Evaluation and Research Agency, Porton Down, Salisbury, Wiltshire, SP4 0JQ, U.K.
Microb Pathog. 1999 Mar;26(3):159-69. doi: 10.1006/mpat.1998.0261.
The pathogenic Yersiniae produce a range of virulence proteins, encoded by a 70 kb plasmid, which are essential for infection, and also form part of a contact-dependent virulence mechanism. One of these proteins, V antigen, has been shown to confer a high level of protection against parenteral infection with Y. pestis in murine models, and is considered to be a protective antigen. In this study, the protective efficacy of V antigen has been compared in the same model with that of other proteins (YopE, YopK and YopN), which are part of the contact-dependent virulence mechanism. Mice immunised with two intraperitoneal doses of V antigen or each of the Yops, administered with either Alhydrogel or interleukin-12, produced high antigen-specific serum IgG titres. As shown in previous studies, V+Alhydrogel was fully protective, and 5/5 mice survived a subcutaneous challenge with 90 or 9x10(3) LD50's of Y. pestis GB. In addition, these preliminary studies also showed that V+IL-12 was partially protective: 4/5 or 3/5 mice survived a challenge with 90 or 9x10(3) LD50's, respectively. In contrast, none of the mice immunised with the Yops survived the challenges, and there was no significant delay in the mean time to death compared to mice receiving a control protein. These results show that using two different vaccine regimens, Yops E, K and N, failed to elicit protective immune responses in a murine model of plague, whereas under the same conditions, V antigen was fully or partially protective.
致病性耶尔森菌产生一系列毒力蛋白,由一个70 kb的质粒编码,这些蛋白对感染至关重要,也是接触依赖性毒力机制的一部分。其中一种蛋白,V抗原,已被证明在小鼠模型中对鼠疫耶尔森菌的肠道外感染具有高水平的保护作用,被认为是一种保护性抗原。在本研究中,在同一模型中比较了V抗原与其他蛋白(YopE、YopK和YopN)的保护效果,这些蛋白是接触依赖性毒力机制的一部分。用两剂腹腔注射V抗原或每种Yop免疫的小鼠,同时给予氢氧化铝或白细胞介素-12,产生了高抗原特异性血清IgG滴度。如先前研究所示,V+氢氧化铝具有完全保护作用,5/5的小鼠在皮下接种90或9×10³个鼠疫耶尔森菌GB半数致死量后存活。此外,这些初步研究还表明,V+白细胞介素-12具有部分保护作用:分别有4/5或3/5的小鼠在接种90或9×10³个半数致死量后存活。相比之下,用Yop免疫的小鼠在接种后无一存活,与接受对照蛋白的小鼠相比,平均死亡时间没有显著延迟。这些结果表明,使用两种不同的疫苗方案,YopE、YopK和YopN未能在鼠疫小鼠模型中引发保护性免疫反应,而在相同条件下,V抗原具有完全或部分保护作用。