Center for Infectious Diseases and Vaccinology, Biodesign Institute at Arizona State University, Tempe, AZ 85287, USA and Dept of Basic Medical Sciences, The University of Arizona College of Medicine-Phoenix in Partnership with Arizona State University, Phoenix, AZ 85004, USA.
Expert Rev Vaccines. 2010 Mar;9(3):299-307. doi: 10.1586/erv.09.163.
Noroviruses (NoV) cause the great majority of epidemic nonbacterial gastroenteritis in humans. Expression of the capsid protein in recombinant systems, including insect and plant cells, yields assembly of virus-like particles (VLPs) that mimic the antigenic structure of authentic virions, and are relatively acid- and heat-stable. Norwalk virus (NV), the prototype NoV, has been studied extensively, and Norwalk virus-like particles (NVLPs) produced in insect cells and plants are immunogenic in mice and humans when delivered orally, stimulating the production of systemic and mucosal anti-NV antibodies. NVLPs are also highly immunogenic when delivered intranasally, provoking antibodies at levels similar to orally delivered VLP at much lower doses. Oral and nasal delivery of NVLPs efficiently produces antibodies at distal mucosal sites, which suggests that NVLPs could be used to deliver heterologous peptide antigens by production of genetic fusion chimeric capsid proteins. Examination of norovirus VLP surface structures and receptor binding motifs facilitates identification of potential sites for insertion of foreign peptides that will minimally affect the efficiency of VLP assembly and receptor binding. Thus, there is strong potential to use norovirus VLPs as vaccine-delivery vehicles.
诺如病毒(NoV)是引起人类大多数爆发性非细菌性胃肠炎的主要病原体。在重组系统(包括昆虫细胞和植物细胞)中表达衣壳蛋白可组装成类似病毒粒子的病毒样颗粒(VLPs),这些颗粒具有相对耐酸和耐热的特性。诺如病毒(NV)是 NoV 的原型病毒,已被广泛研究,当以口服方式给予时,在昆虫细胞和植物中产生的诺如病毒样颗粒(NVLPs)在小鼠和人类中具有免疫原性,可刺激产生系统和黏膜抗 NV 抗体。NVLPs 经鼻内给药也具有高度免疫原性,可引发与口服给药 VLP 相似水平的抗体,但所需剂量要低得多。NVLPs 的口服和鼻内给药可有效地在远端黏膜部位产生抗体,这表明 NVLPs 可通过产生遗传融合嵌合衣壳蛋白来递呈异源肽抗原。对诺如病毒 VLP 表面结构和受体结合基序的研究有助于确定可插入外源肽的潜在部位,这些外源肽的插入最小程度地影响 VLP 组装和受体结合的效率。因此,诺如病毒 VLPs 具有作为疫苗传递载体的巨大潜力。