Epstein M A
Proc R Soc Lond B Biol Sci. 1987 Mar 23;230(1259):147-61. doi: 10.1098/rspb.1987.0014.
Carcinogenic viruses have been discovered in numerous animal species over the last 80 years but their role in human cancer has only recently become an important issue. With EB virus involved with endemic Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma, hepatitis B virus with primary liver cancer, papilloma viruses with carcinoma of the cervix, and T-cell leukaemia virus with adult T leukaemia, 20-25% of all human cancer appears to have a virus component in its causation. By analogy with certain virus-induced animal cancers, vaccine prevention of infection should greatly reduce subsequent tumour development; vaccines against hepatitis B virus are already on trial for this purpose in populations at risk. Experiments are described in which an EB virus subunit vaccine consisting of the virus-determined membrane antigen glycoprotein molecule of molecular mass 340 kDa (MA gp340) has been prepared by two purification methods. Material from one of these has successfully protected cotton-top tamarins against a 100% lymphomagenic dose of challenge virus and investigations are under way to identify an immunogen, based on MA gp340, suitable for use in man. Genetically engineered bacterial, yeast, and mammalian cells expressing the gp340 gene are already available; this gene has also been inserted into vaccinia and varicella virus vectors. Powerful new adjuvants are also considered, together with future strategies for human vaccine studies.
在过去80年里,已在众多动物物种中发现致癌病毒,但它们在人类癌症中的作用直到最近才成为一个重要问题。EB病毒与地方性伯基特淋巴瘤和未分化鼻咽癌有关,乙型肝炎病毒与原发性肝癌有关,乳头瘤病毒与宫颈癌有关,T细胞白血病病毒与成人T白血病有关,所有人类癌症中约20%-25%的病因似乎都有病毒成分。类比某些病毒诱导的动物癌症,通过疫苗预防感染应能大大减少后续肿瘤的发生;针对乙型肝炎病毒的疫苗已在高危人群中进行此类试验。本文描述了实验过程,其中通过两种纯化方法制备了一种EB病毒亚单位疫苗,该疫苗由分子量为340 kDa的病毒决定膜抗原糖蛋白分子(MA gp340)组成。其中一种方法获得的材料已成功保护棉顶狨猴免受100%致淋巴瘤剂量的攻击病毒感染,目前正在进行研究以确定一种基于MA gp340的、适用于人类的免疫原。现已获得表达gp340基因的基因工程细菌、酵母和哺乳动物细胞;该基因也已插入痘苗病毒和水痘病毒载体中。还考虑了强大的新型佐剂以及人类疫苗研究的未来策略。