A genetically-defined riboflavin auxotroph of Actinobacillus pleuropneumoniae as a live attenuated vaccine
A genetically-defined riboflavin auxotroph of Actinobacillus pleuropneumoniae as a live attenuated vaccine
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DOI：
10.1016/s0264-410x(00)00076-1
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发表时间：
2000-06-15
期刊：
影响因子：
5.5
通讯作者：
Mulks, MH
中科院分区：
文献类型：
--
作者：
Fuller, TE;Thacker, BJ;Mulks, MH
胸膜肺炎放线杆菌是一种革兰氏阴性多形性杆菌，是猪中严重、高度传染性且常常致命的胸膜肺炎的病原体。我们之前报道过通过用编码卡那霉素抗性的抗生素盒替换 APP 核黄素生物合成操纵子 (ribGBAH) 的一部分来构建遗传定义的稳定核黄素营养缺陷型细胞，并证明这种核黄素营养缺陷型细胞是无毒的。在这项研究中，我们评估了胸膜肺炎放线菌核黄素营养缺陷型刺激针对胸膜肺炎的保护性免疫的能力。最初的攻击实验表明，与气管内免疫或在不存在外源核黄素的情况下用活细菌进行肌内免疫相比，在包含限量外源核黄素的疫苗制剂中使用活的减毒血清型1A rib突变体进行肌内疫苗接种，可以更好地防止强毒性胸膜肺炎放线菌的攻击。随后的研究表明，疫苗接种剂量、外源核黄素浓度和疫苗株血清型各不相同，用无毒力核黄素营养缺陷型活菌进行免疫可以对同源和异源胸膜肺炎放线菌强毒血清型的实验攻击产生显着的保护作用。 (C) 2000 Elsevier Science Ltd. 保留所有权利。
Actinobacillus pleuropneumoniae is a gram negative pleiomorphic rod that is the causative agent of a severe, highly infectious and often fatal pleuropneumonia in swine. We have previously reported the construction of genetically-defined stable riboflavin auxotrophs by replacement of a portion of the APP riboflavin biosynthetic operon (ribGBAH) with an antibiotic cassette encoding resistance to kanamycin, and have demonstrated that such riboflavin auxotrophs are avirulent. In this study, we evaluated riboflavin auxotrophs of A. pleuropneumoniae for their ability to stimulate protective immunity against pleuropneumonia. An initial challenge experiment demonstrated that intramuscular Vaccination with a live attenuated serotype 1A rib mutant, in a vaccine formulation that included a limiting amount of exogenous riboflavin, provided better protection against challenge with virulent A. pleuropneumoniae than either intratracheal immunization or intramuscular immunization with live bacteria in the absence of exogenous riboflavin. Subsequent studies in which the vaccine inoculating dose, concentration of exogenous riboflavin, and serotype of the vaccine strain were varied demonstrated that immunization with live avirulent riboflavin auxotrophs could elicit significant protection against experimental challenge with both homologous and heterologous virulent serotypes of A. pleuropneumoniae. (C) 2000 Elsevier Science Ltd. All rights reserved.