Ball J M, Hardy M E, Atmar R L, Conner M E, Estes M K
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.
J Virol. 1998 Feb;72(2):1345-53. doi: 10.1128/JVI.72.2.1345-1353.1998.
Recombinant Norwalk virus-like particles (rNV VLPs) produced in insect cells were evaluated as an oral immunogen in CD1 and BALB/c mice by monitoring rNV-specific serum total and subclass immunoglobulin G (IgG) and intestinal IgA responses. Dose and kinetics of response were evaluated in the presence and absence of the mucosal adjuvant cholera toxin (CT). rNV-specific serum IgG and intestinal IgA were detected in the absence of CT, and the number of responders was not significantly different from that of mice administered VLPs with CT at most doses. The use of CT was associated with induction of higher levels of IgG in serum; this effect was greater at higher doses of VLPs. IgG in serum was detected in the majority of animals by 9 days postimmunization (dpi), and intestinal IgA responses were detected by 24 dpi. In the absence of CT, IgG2b was the dominant IgG subclass response in both mouse strains. Thus, nonreplicating rNV VLPs are immunogenic when administered orally in the absence of any delivery system or mucosal adjuvant. These studies demonstrate that rNV VLPs are an excellent model to study the oral delivery of antigen, and they are a potential mucosal vaccine for NV infections.
通过监测重组诺如病毒特异性血清总免疫球蛋白G（IgG）和亚类免疫球蛋白G以及肠道IgA反应，评估了在昆虫细胞中产生的重组诺如病毒样颗粒（rNV VLPs）作为CD1和BALB/c小鼠口服免疫原的效果。在存在和不存在黏膜佐剂霍乱毒素（CT）的情况下评估了反应的剂量和动力学。在不存在CT的情况下检测到了rNV特异性血清IgG和肠道IgA，并且在大多数剂量下，反应小鼠的数量与给予含CT的VLPs的小鼠数量没有显著差异。CT的使用与血清中更高水平IgG的诱导相关；在更高剂量的VLPs下这种效应更明显。在免疫后9天（dpi），大多数动物的血清中检测到了IgG，在24 dpi时检测到了肠道IgA反应。在不存在CT的情况下，IgG2b是两种小鼠品系中主要的IgG亚类反应。因此，在不存在任何递送系统或黏膜佐剂的情况下口服给药时，非复制性rNV VLPs具有免疫原性。这些研究表明，rNV VLPs是研究抗原口服递送的优秀模型，并且它们是用于诺如病毒感染的潜在黏膜疫苗。
