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Engineering of a novel oral herpesvirus vaccine using a gene therapy

使用基因疗法设计新型口服疱疹病毒疫苗

基本信息

批准号：
09670238
负责人：
IRIE Hiroshi
金额：
$ 2.05万
依托单位：
Teikyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670238/
关键词：
Herpes simplex virus oral vaccine gene therapy epitope エビトープ

项目摘要

The development of prophylactic and therapeutic vaccine against human virus infection represents the best hope for controlling the continuing and devasting worldwide herpes endemic. A successful preventative herpesvirus vaccine should induce both systemic and mucosal protective immunity. We have already described the possibility of oral immunization with live HSV-1 as a vaccine and have presented evidence suggesting that the best immunization method for preventing the virus infection rather than other routes such as cutaneous or intravenous ones. Oral administration induces the anti-HSV-1 antibody on the mucosal surfaces where most virus enter the body, as well as provides systemic immunity.Further work will be required to optimize the conditions of immunization and to explore the use of safer immunogens. This study designed to develop the oral engineering of recombinant live vectors such as vaccinia expressing the subcomponent of HSV-1 that induce cellular and humoral immunity against herpesvirus infection. Bands of oral immunized antibody are fewer than those of intraperitoneal immunized antibody by western blotting, mainly two bands (130K and 64K daltons). Band of 64K corresponds to glycoproteins D of herpesvirus and one of 130K may be glycoprotein B. It was demonstrated that these glycoproteins are stable in oral administration and they are also candidates for a recombinant subcomponent of oral vaccine.We made the recombinant vaccinia virus expressing HSV-1 glycoprotin B and D. The survival rates of mice orally immunized with glycoprotein B, D and both of them were 20%, 30% and 40% respectively after HSV-1 lethal challenge. But, these rates are lower than the survival rate of mice orally live administered with live virus. Probably, cellular immunity participates considerably in this immunity. Effective factor of cellular immunity are remaining problem in this protection in the future.

人类疱疹病毒感染的预防性和治疗性疫苗的研制是控制世界范围内持续和毁灭性的疱疹流行病的最大希望。一个成功的预防性疱疹病毒疫苗应诱导全身和粘膜保护性免疫。我们已经描述了用活HSV-1作为疫苗进行口服免疫的可能性，并提出了证据，表明预防病毒感染的最佳免疫方法，而不是其他途径，如皮肤或静脉注射。口服给药可在大多数病毒进入体内的粘膜表面诱导抗HSV-1抗体，并提供全身免疫。本研究旨在开发表达HSV-1亚组分的重组活载体如牛痘的口服工程，以诱导抗疱疹病毒感染的细胞和体液免疫。经口免疫的抗体蛋白质条带数少于腹腔免疫的抗体，主要为130 K和64 K两条带。64 K带对应疱疹病毒糖蛋白D，130 K带之一可能为糖蛋白B。本研究制备了表达HSV-1糖蛋白B和D的重组痘苗病毒，并对重组痘苗病毒的免疫原性进行了研究。口服糖蛋白B、D及两者联合免疫的小鼠经HSV-1致死攻击后存活率分别为20%、30%和40%。但是，这些比率低于口服活病毒的小鼠的存活率。很可能，细胞免疫在很大程度上参与了这种免疫。细胞免疫的有效因素是今后这一保护中有待解决的问题。