Jagadish M N, Edwards S J, Hayden M B, Grusovin J, Vandenberg K, Schoofs P, Hamilton R C, Shukla D D, Kalnins H, McNamara M, Haynes J, Nisbet I T, Ward C W, Pye D
CSIRO, Division of Biomolecular Engineering, Parkville, Victoria, Australia.
Intervirology. 1996;39(1-2):85-92. doi: 10.1159/000150479.
Presentation of subunit vaccines in a highly ordered aggregate form can result in enhanced immune responses. Coat protein (CP) monomers of a potyvirus (Johnsongrass mosaic virus) when produced in heterologous host expression systems (Escherichia coli, yeast and insect cells) self-polymerized to produce potyvirus-like particles (PVLPs). The N- and C-terminal regions of potyvirus CP are surface-exposed and are not required for assembly. Hybrid CP monomers containing short peptides fused to their N- and/or C-termini, or large target antigens fused to the N-terminus or replacing most of the N- or C-terminal exposed regions retained the ability to assemble into hybrid PVLPs. Such chimeric PVLPs were highly immunogenic in mice and rabbits even in the absence of any adjuvant. Potyvirus CP is highly versatile in accommodating peptides or large antigens and is able to present antigens exposed on the surface of virus-like particles. This, combined with the efficiency of high level bacterial and insect cell expression systems, makes PVLPs an attractive non-pathogenic and non-replicative vaccine carrier.
以高度有序的聚集体形式呈现亚单位疫苗可增强免疫反应。马铃薯Y病毒属病毒(约翰逊草花叶病毒)的外壳蛋白(CP)单体在异源宿主表达系统(大肠杆菌、酵母和昆虫细胞)中产生时会自我聚合,形成类马铃薯Y病毒颗粒(PVLP)。马铃薯Y病毒CP的N端和C端区域暴露于表面,组装时不需要它们。含有融合至其N端和/或C端的短肽的杂合CP单体,或融合至N端或取代大部分N端或C端暴露区域的大的靶抗原,保留了组装成杂合PVLP的能力。即使在没有任何佐剂的情况下,这种嵌合PVLP在小鼠和兔子中也具有高度免疫原性。马铃薯Y病毒CP在容纳肽或大抗原方面具有高度通用性,并且能够呈递暴露于病毒样颗粒表面的抗原。这与高效的高水平细菌和昆虫细胞表达系统相结合,使PVLP成为一种有吸引力的非致病性和非复制性疫苗载体。