Saif L, Yuan L, Ward L, To T
Department of Veterinary Preventive Medicine, Ohio Agricultural Research and Development Center, Ohio State University, Wooster 44691, USA.
Adv Exp Med Biol. 1997;412:397-403. doi: 10.1007/978-1-4899-1828-4_62.
Gnotobiotic piglets serve as a useful animal model for studies of rotavirus pathogenesis and immunity. An advantage over laboratory animal models is the prolonged susceptibility of piglets to rotavirus-induced disease, permitting an analysis of cross-protection and active immunity. Studies from our laboratory of the pathogenesis of human rotavirus infections in gnotobiotic piglets have confirmed that villous atrophy is induced in piglets given virulent but not attenuated human rotavirus (Wa strain) and have revealed that factors other than villous atrophy may contribute to the early diarrhea induced. To facilitate and improve rotavirus vaccination strategies, it is important to identify correlates of protective immunity. Comparison of antibody immune responses induced by infection with virulent porcine and human rotaviruses (mimic host response to natural infection) with those induced by live attenuated human rotavirus (mimic attenuated oral vaccines) in the context of homotypic protection has permitted an analysis of correlates of protective immunity. Our results indicate that the magnitude of the immune response is greatest in lymphoid tissues adjacent to the site of viral replication (small intestine). Secondly there was a direct association between the degree of protection induced and the level of the intestinal immune response, with primary exposure to virulent rotaviruses inducing significantly higher numbers of IgA ASC and complete protection against challenge. These studies thus have established basic parameters related to immune protection in the piglet model of rotavirus-induced disease, verifying the usefulness of this model to apply new strategies for the design and improvement of rotavirus vaccines.
无菌仔猪是研究轮状病毒发病机制和免疫的有用动物模型。与实验室动物模型相比，其优势在于仔猪对轮状病毒诱导疾病的易感性持续时间更长，这有利于分析交叉保护和主动免疫。我们实验室对无菌仔猪中人轮状病毒感染发病机制的研究证实，给仔猪接种强毒株而非减毒株人轮状病毒（Wa株）会导致绒毛萎缩，并且发现除绒毛萎缩外的其他因素可能导致早期腹泻。为了促进和改进轮状病毒疫苗接种策略，识别保护性免疫的相关因素很重要。在同型保护的背景下，比较强毒株猪轮状病毒和人轮状病毒感染诱导的抗体免疫反应（模拟宿主对自然感染的反应）与减毒活疫苗人轮状病毒诱导的抗体免疫反应（模拟减毒口服疫苗），有助于分析保护性免疫的相关因素。我们的结果表明，免疫反应的强度在病毒复制部位（小肠）附近的淋巴组织中最大。其次，诱导的保护程度与肠道免疫反应水平之间存在直接关联，初次接触强毒株轮状病毒会诱导产生显著更多的IgA ASC，并对攻毒提供完全保护。因此，这些研究确立了轮状病毒诱导疾病仔猪模型中与免疫保护相关的基本参数，验证了该模型在应用新策略设计和改进轮状病毒疫苗方面的实用性。
