Bacterial Diseases Branch, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, United States.
Enteric Diseases Branch, Naval Medical Research Center (NMRC), 503 Robert Grant Avenue, Silver Spring, MD 20910, United States.
Vaccine. 2014 Mar 26;32(15):1754-60. doi: 10.1016/j.vaccine.2013.12.068. Epub 2014 Feb 9.
Live oral monovalent Shigella flexneri 2a vaccine candidates as well as bivalent formulations with Shigella sonnei were evaluated in a rhesus monkey model for colonization and immunogenicity. Freshly harvested suspensions of S. flexneri 2a vaccine candidates WRSf2G12 and WRSf2G15 as well as S. sonnei vaccine candidate WRSs3 were nasogastrically administered to groups of rhesus monkeys, Macaca mulatta, either in a monovalent form or when combined with each other. The animals were monitored daily for physical well-being, stools were subjected to quantitative colony immunoblot assays for bacterial excretion and blood and stools were evaluated for humoral and mucosal immune responses. No clinical symptoms were noted in any group of animals and the vaccine candidates were excreted robustly for 48-72h without significant changes in either the magnitude or duration of excretion when given as a monovalent or as bivalent mixtures. Similarly, immunological interferences were not apparent in the magnitude of humoral and mucosal immune responses observed toward Shigella-specific antigens when monkeys were fed monovalent or bivalent formulations. These results predict that a multivalent live oral vaccine of more than one serotype can have a favorable outcome for protection against shigellosis.
在恒河猴模型中评估了口服单价福氏志贺菌 2a 活疫苗候选物以及与宋内志贺菌的双价制剂,以评估其定植和免疫原性。新鲜收获的单价福氏志贺菌 2a 疫苗候选物 WRSf2G12 和 WRSf2G15 以及宋内志贺菌疫苗候选物 WRSs3 的混悬液通过鼻胃管给予恒河猴(Macaca mulatta),以单价形式或彼此组合。每天监测动物的身体状况,对粪便进行定量集落免疫印迹分析以检测细菌排泄,对血液和粪便进行体液和黏膜免疫应答评估。任何一组动物均未出现临床症状,疫苗候选物在 48-72 小时内大量排泄,无论作为单价制剂还是双价混合物给药,排泄的幅度或持续时间均无明显变化。同样,当给与单价或双价制剂时,针对志贺菌特异性抗原的体液和黏膜免疫应答的幅度也没有明显的免疫干扰。这些结果预测,针对多种血清型的多价口服活疫苗可能会对志贺菌病的保护产生有利结果。