El-Ghorr A A, Williams R M, Heap C, Norval M
Department of Medical Microbiology, University of Edinburgh Medical School, Teviot Place, EH8 9AG, Edinburgh, UK.
FEMS Immunol Med Microbiol. 2000 Dec;29(4):255-61. doi: 10.1111/j.1574-695X.2000.tb01531.x.
Herpes simplex virus (HSV) is common throughout the world and is a target for vaccine development. Transcutaneous immunisation is a novel technique that uses the application of vaccine antigens in solution on the skin in the presence of cholera toxin (CT) as an adjuvant. This study investigated the potential of transcutaneous immunisation in C3H mice, using CT co-administered with whole inactivated HSV-1 (CT+HSVi) or HSV-1 antigens extracted from infected Vero cells (CT+HSVag) or a control protein (CT+BSA). The application of any of the three vaccines on to bare mouse skin resulted in the migration of Langerhans cells from the epidermis and in the production of serum antibodies to CT. Both HSV preparations generated serum and mucosal (faecal) antibodies to HSV, with the CT+HSVi vaccine being a more potent stimulator of humoral immunity. The CT+HSVag vaccine, however, was the more potent stimulator of cell-mediated immunity, giving rise to a strong delayed type hypersensitivity response and lymphocyte proliferation in vitro. When the mice were challenged by epidermal inoculation of HSV, the CT+HSVag vaccine induced a higher level of protection than the CT+HSVi vaccine, a result which may indicate that the efficacy of HSV vaccines depends on stimulation of cell-mediated rather than humoral responses. The success of topical vaccination suggests that the transcutaneous route may offer a promising potential for novel vaccine delivery which merits further investigation.
单纯疱疹病毒(HSV)在全球范围内普遍存在,是疫苗研发的目标。经皮免疫是一种新技术,它是在霍乱毒素(CT)作为佐剂存在的情况下,将疫苗抗原溶液应用于皮肤。本研究调查了在C3H小鼠中经皮免疫的潜力,使用与全灭活HSV-1共同给药的CT(CT+HSVi)或从感染的Vero细胞中提取的HSV-1抗原(CT+HSVag)或一种对照蛋白(CT+BSA)。将这三种疫苗中的任何一种应用于裸露的小鼠皮肤,都会导致朗格汉斯细胞从表皮迁移,并产生针对CT的血清抗体。两种HSV制剂均产生了针对HSV的血清和黏膜(粪便)抗体,其中CT+HSVi疫苗是体液免疫的更强刺激剂。然而,CT+HSVag疫苗是细胞介导免疫的更强刺激剂,在体外引起强烈的迟发型超敏反应和淋巴细胞增殖。当小鼠通过表皮接种HSV进行攻击时,CT+HSVag疫苗诱导的保护水平高于CT+HSVi疫苗,这一结果可能表明HSV疫苗的疗效取决于细胞介导反应而非体液反应的刺激。局部接种疫苗的成功表明,经皮途径可能为新型疫苗递送提供有前景的潜力,值得进一步研究。