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用表达单纯疱疹病毒糖蛋白B的重组腺病毒进行鼻内免疫后的黏膜免疫与保护作用

Mucosal immunity and protection after intranasal immunization with recombinant adenovirus expressing herpes simplex virus glycoprotein B.

作者信息

Gallichan W S, Johnson D C, Graham F L, Rosenthal K L

机构信息

Department of Pathology, McMaster University Health Sciences Centre, Hamilton, Canada.

出版信息

J Infect Dis. 1993 Sep;168(3):622-9. doi: 10.1093/infdis/168.3.622.

Abstract

A recombinant adenovirus (Ad) expressing glycoprotein B (gB) of herpes simplex virus (HSV) type 1 (AdgB8) was evaluated as a mucosal vaccine candidate. When administered intranasally (inl) to C57B1/6 mice, AdgB8 induced levels of serum anti-HSV gB IgG antibodies similar to those of mice immunized intraperitoneally (ip), which neutralized both HSV-1 and -2. Mice immunized inl with AdgB8 produced secretory IgA specific for HSV gB, but mice immunized ip did not. Splenic anti-HSV cytotoxic T lymphocytes (CTL) were observed after inl and ip immunization; however, there was a time-dependent decrease in the anti-HSV CTL activity from spleens of inl immunized mice. Anti-HSV CTL were also present in the mediastinal lymph nodes after inl but not ip AdgB8 immunization. Furthermore, mice immunized inl with AdgB8 were protected against heterologous inl challenge with HSV-2, and this protection lasted longer than in ip-immunized mice. These results indicate that mucosal immunization with a recombinant adenovirus can induce mucosal and systemic immune responses and provide long-term protection from mucosally or sexually transmitted viruses.

摘要

一种表达1型单纯疱疹病毒(HSV)糖蛋白B(gB)的重组腺病毒(Ad)(AdgB8)被评估为一种黏膜疫苗候选物。当经鼻内(inl)给予C57B1/6小鼠时,AdgB8诱导产生的血清抗HSV gB IgG抗体水平与经腹腔内(ip)免疫的小鼠相似,该抗体可中和HSV - 1和HSV - 2。经inl用AdgB8免疫的小鼠产生了针对HSV gB的分泌型IgA,而经ip免疫的小鼠则未产生。在inl和ip免疫后均观察到脾脏抗HSV细胞毒性T淋巴细胞(CTL);然而,inl免疫小鼠脾脏中的抗HSV CTL活性存在时间依赖性下降。在inl给予AdgB8免疫后,纵隔淋巴结中也存在抗HSV CTL,但经ip免疫的小鼠则没有。此外,经inl用AdgB8免疫的小鼠对HSV - 2的异源inl攻击具有保护作用,且这种保护作用持续的时间比经ip免疫的小鼠更长。这些结果表明,用重组腺病毒进行黏膜免疫可诱导黏膜和全身免疫反应,并为预防经黏膜或性传播的病毒提供长期保护。

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