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表达三种不同单纯疱疹病毒糖蛋白的质粒疫苗的抗体反应及保护能力

Antibody response and protective capacity of plasmid vaccines expressing three different herpes simplex virus glycoproteins.

作者信息

Nass P H, Elkins K L, Weir J P

机构信息

Laboratory of DNA Viruses, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA.

出版信息

J Infect Dis. 1998 Sep;178(3):611-7. doi: 10.1086/515374.

Abstract

Plasmid expression vectors were constructed that contained the genes encoding herpes simplex virus 1 (HSV-1) glycoproteins C (gC), D (gD), and E (gE). Mice receiving two intramuscular injections of expression plasmid (50 microg) produced a specific HSV-1 antibody response. Mice receiving the gD plasmid were protected against a lethal intraperitoneal challenge of HSV-1 (5 x 10(4) pfu) but not against more demanding challenge doses. Protection with gC or gE plasmid vaccination could be demonstrated only if the inoculating dose of DNA was increased to 250 microg. In contrast, all mice immunized with vaccinia recombinants expressing either gC or gE survived HSV-1 challenge. Analysis of the HSV-1 antibody isotype produced by plasmid immunization revealed a response dominated by IgG2a. Combination delivery of all three glycoprotein expression plasmids provided better protection against lethal challenge, but mice receiving the combination were still not able to withstand increased challenge doses of virus.

摘要

构建了包含编码单纯疱疹病毒1型(HSV-1)糖蛋白C(gC)、D(gD)和E(gE)基因的质粒表达载体。接受两次肌肉注射表达质粒(50微克)的小鼠产生了特异性HSV-1抗体反应。接受gD质粒的小鼠对HSV-1的致死性腹腔攻击(5×10⁴ 蚀斑形成单位)具有抵抗力,但对要求更高的攻击剂量则没有抵抗力。只有当DNA接种剂量增加到250微克时,才能证明用gC或gE质粒疫苗接种具有保护作用。相比之下,所有用表达gC或gE的痘苗重组体免疫的小鼠在HSV-1攻击中存活下来。对质粒免疫产生的HSV-1抗体亚型的分析显示,反应以IgG2a为主。三种糖蛋白表达质粒的联合递送对致死性攻击提供了更好的保护,但接受联合质粒的小鼠仍然无法承受增加的病毒攻击剂量。

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