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杆状病毒重组体表达的马尔堡病毒糖蛋白的抗原性及疫苗潜力

Antigenicity and vaccine potential of Marburg virus glycoprotein expressed by baculovirus recombinants.

作者信息

Hevey M, Negley D, Geisbert J, Jahrling P, Schmaljohn A

机构信息

Virology Division, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, Frederick, Maryland 21702, USA.

出版信息

Virology. 1997 Dec 8;239(1):206-16. doi: 10.1006/viro.1997.8883.

Abstract

There is no effective vaccine for Marburg virus (MBGV) or any other filovirus, nor enough pertinent information to expedite rational vaccine development. To ascertain some of the minimal requirements for a MBGV vaccine, we determined whether whole inactivated MBGV, or a baculovirus-expressed virion subunit, could be used to immunize guinea pigs against a lethal infection. Baculovirus recombinants were made to express the MBGV glycoprotein (GP) either as a full-length, cell-associated molecule or a slightly truncated (5.4%) product secreted into medium; the latter, for its far greater ease in manipulation, was tested for its vaccine potential. Like MBGV GP, both the full-length and truncated GP expressed by baculovirus recombinants were abundantly glycosylated with both N- and O-linked glycans; differences in glycosylation were detectable, but these could not be shown to affect antigenicity with respect to available antibodies. The recombinant truncated glycoprotein elicited protection against lethal challenge with the MBGV isolate from which it was constructed and less effectively against an antigenically disparate MBGV isolate. Killed (irradiated) MBGV antigen was protective, in a reciprocal fashion, against both MBGV types. In a preliminary assessment of possible protective mechanisms, serum antibodies from immune animals were shown to be sufficient for protecting naive guinea pigs from lethal MBGV infections

摘要

目前尚无针对马尔堡病毒(MBGV)或任何其他丝状病毒的有效疫苗,也没有足够的相关信息来加速合理的疫苗开发。为了确定MBGV疫苗的一些最低要求,我们研究了全灭活的MBGV或杆状病毒表达的病毒粒子亚基是否可用于免疫豚鼠以抵抗致死性感染。构建杆状病毒重组体以表达全长的、与细胞相关的MBGV糖蛋白(GP)分子或分泌到培养基中的略微截短(5.4%)的产物;由于后者在操作上更为简便,因此对其疫苗潜力进行了测试。与MBGV GP一样,杆状病毒重组体表达的全长和截短的GP都大量糖基化,同时具有N-连接和O-连接聚糖;糖基化存在差异,但就现有抗体而言,这些差异并未显示出对抗原性有影响。重组截短糖蛋白对构建它所使用的MBGV分离株的致死性攻击具有保护作用,而对抗原性不同的MBGV分离株的保护作用较弱。灭活(辐照)的MBGV抗原以相互的方式对两种MBGV类型都具有保护作用。在对可能的保护机制进行的初步评估中,免疫动物的血清抗体足以保护未感染的豚鼠免受致死性MBGV感染。

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