Oral immunization of mice with the live vaccine strain (LVS) of Francisella tularensis protects mice against respiratory challenge with virulent type A F. tularensis
Oral immunization of mice with the live vaccine strain (LVS) of Francisella tularensis protects mice against respiratory challenge with virulent type A F. tularensis
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DOI：
10.1016/j.vaccine.2007.02.014
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发表时间：
2007-05-10
期刊：
影响因子：
5.5
通讯作者：
Chen, Wangxue
中科院分区：
文献类型：
--
作者：
KuoLee, Rhonda;Harris, Greg;Chen, Wangxue
图拉氏方济氏菌是一种革兰氏阴性胞内细菌，是图拉热病的病原体。这种感染可通过各种途径引起，并可表现为几种临床形式，其中由吸入引起的播散性伤寒形式最为致命。近50年前开发的减毒活疫苗株(LVS)仍然是唯一有效的图拉热病疫苗，它仍然只作为高危个体的研究新药可用。这种疫苗，当通过刮除接种时，似乎对随后的系统感染提供了坚实的保护，但对呼吸道感染的效果并不令人满意。在这项研究中，我们在图拉热症小鼠模型上评估了LVS口服免疫对图拉氏菌强毒株引起的全身和呼吸道感染的保护作用。口服LVS免疫可有效保护Balb/c小鼠免受A型和B型图拉氏丝虫致死性全身或呼吸道攻击。与假免疫的小鼠相比，口服LVS免疫的小鼠在肺和脾中的毒力图拉氏丝虫的负担显著减少，肝脏的组织损伤和炎症也较轻。免疫诱导血清和支气管肺泡灌洗液中的图拉氏丝虫特异性抗体反应，以及抗原特异性的脾细胞增殖和干扰素-γ和IL-2的产生。保护效果与免疫剂量大小有关，与免疫剂量无关。与其他途径免疫小鼠一样，口服免疫诱导的保护性免疫是相对短暂的。这些结果表明，应该进一步探索口服免疫作为对抗图拉热症的替代疫苗接种策略。(C)2007爱思唯尔有限公司。保留所有权利。
Francisella tularensis is a Gram-negative intracellular bacterium, and the causative agent of tularemia. The infection can be initiated by various routes and can manifest itself in several clinical forms with the disseminated typhoidal form initiated by inhalation being most fatal. The attenuated live vaccine strain (LVS), developed almost 50 years ago, remains the sole effective tularemia vaccine, which is still only available as an investigational new drug for at-risk individuals. This vaccine, when given by scarification, appears to provide solid protection against subsequent systemic infection with clinical strains of F. tularensis, but its efficacy against respiratory infection is less satisfactory. In this study, we evaluated the potential of oral immunization with LVS for eliciting protection against systemic and respiratory infection with virulent F. tularensis strains in a mouse model of tularemia. Oral LVS immunization was highly effective at protecting Balb/c mice against lethal systemic or respiratory challenges with type A and type B F. tularensis. Compared to sham-immunized mice, oral LVS-immunized mice showed significant reductions in burdens of virulent F. tularensis in the lung and spleen and milder tissue damage and inflammation in the liver. The immunization induced F. tularensis-specific antibody responses in the serum and bronchoalveolar lavage fluids, as well as antigen-specific splenocyte proliferation and IFN-gamma and IL-2 production. The protective efficacy was related to the size of the immunizing dose but not the number of doses administered. Like other routes of LVS immunization in mice, the protective immunity induced by oral immunization was relatively short-lived. These results suggest that oral immunization should be explored further as an alternative vaccination strategy to combat tularemia. (C) 2007 Elsevier Ltd. All rights reserved.