Schmaljohn C S, Chu Y K, Schmaljohn A L, Dalrymple J M
Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21701-5011.
J Virol. 1990 Jul;64(7):3162-70. doi: 10.1128/JVI.64.7.3162-3170.1990.
Baculovirus and vaccinia virus vectors were used to express the small (S) and medium (M) genome segments of Hantaan virus. Expression of the complete S or M segments yielded proteins electrophoretically indistinguishable from Hantaan virus nucleocapsid protein or envelope glycoproteins (G1 and G2), and expression of portions of the M segment, encoding either G1 or G2 alone, similarly yielded proteins which closely resembled authentic Hantaan virus proteins. The expressed envelope proteins retained all antigenic sites defined by a panel of monoclonal antibodies to Hantaan virus G1 and G2 and elicited antibodies in animals which reacted with authentic viral proteins. A Hantaan virus infectivity challenge model in hamsters was used to assay induction of protective immunity by the recombinant-expressed proteins. Recombinants expressing both G1 and G2 induced higher titer antibody responses than those expressing only G1 or G2 and protected most animals from infection with Hantaan virus. Baculovirus recombinants expressing only nucleocapsid protein also appeared to protect some animals from challenge. Passively transferred neutralizing monoclonal antibodies similarly prevented infection, suggesting that an antibody response alone is sufficient for immunity to Hantaan virus.
杆状病毒和痘苗病毒载体被用于表达汉坦病毒的小(S)基因组片段和中(M)基因组片段。完整的S或M片段的表达产生的蛋白质在电泳上与汉坦病毒核衣壳蛋白或包膜糖蛋白(G1和G2)无法区分,并且仅编码G1或G2的M片段部分的表达同样产生了与天然汉坦病毒蛋白非常相似的蛋白质。所表达的包膜蛋白保留了由一组针对汉坦病毒G1和G2的单克隆抗体所定义的所有抗原位点,并在动物体内引发了与天然病毒蛋白发生反应的抗体。利用仓鼠的汉坦病毒感染性攻击模型来检测重组表达蛋白诱导的保护性免疫。表达G1和G2的重组体诱导的抗体反应滴度高于仅表达G1或G2的重组体,并保护大多数动物免受汉坦病毒感染。仅表达核衣壳蛋白的杆状病毒重组体似乎也能保护一些动物免受攻击。被动转移的中和性单克隆抗体同样能预防感染,这表明仅抗体反应就足以对汉坦病毒产生免疫。