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[提高疫苗免疫原性的方法]

[Methods for increasing the immunogenicity of vaccines].

作者信息

Kündig T M

机构信息

Dermatologische Klinik, UniversitätsSpital Zürich.

出版信息

Praxis (Bern 1994). 2000 Sep 14;89(37):1477-84.

Abstract

In the past years, enormous efforts have been undertaken to develop vaccine strategies against cancer. The aim is to have the immune system generate what are called killer cells that can specifically recognize the tumor. The surface of tumor cells contains MHC/HLA antigens which present short-chain peptides of tumor specific antigens. A large number of these oligopeptide antigens have been characterized in recent years. They are now available for use as tumor-specific vaccines. The problem is, however, that the immune response of producing T killer cells is very inefficient when these oligopeptide antigens are injected. As the physiological function of these killer cells virus-infected cells, a process associated with substantial tissue damage, the immune system has learned to use these killer cells with reticence over the course of evolution, in other words, when the life of the host is threatened. This does not happen until pathogens start to spread via lymphogenous or hematogenous pathways. And then it takes a certain amount of time after the invader is present for replication to take place. Since the oligopeptide antigens used as vaccines have a very short half-life in the tissue, not enough of them get to the lymph nodes and stay there for enough time to efficiently induce an immune response. Using a mouse model, we were able to show that the efficiency of the vaccine can be increased a million-fold by directly injecting the vaccine into a lymph node or the spleen which imitates lymphogenous or hematogenous spread. The efficiency of the "inactivated vaccine" can be enhanced even more by continuous administration of the vaccine over several days, simulating an especially dangerous virus replication. The evidence gathered in this mouse model was transferred to a clinical trial. The melanoma-specific inactivated vaccine is infused directly into a lymph node of tumor patients. The infusion is continued for several days. Booster vaccines are given every two weeks.

摘要

在过去几年中,人们为开发抗癌疫苗策略付出了巨大努力。目标是让免疫系统产生所谓的杀伤细胞,这些细胞能够特异性识别肿瘤。肿瘤细胞表面含有MHC/HLA抗原,这些抗原呈递肿瘤特异性抗原的短链肽。近年来,大量此类寡肽抗原已得到鉴定。它们现在可作为肿瘤特异性疫苗使用。然而,问题在于,当注射这些寡肽抗原时,产生T杀伤细胞的免疫反应效率非常低。由于这些杀伤细胞对病毒感染细胞具有生理功能,这一过程会导致大量组织损伤,在进化过程中,免疫系统学会谨慎使用这些杀伤细胞,也就是说,只有在宿主生命受到威胁时才会使用。直到病原体开始通过淋巴或血行途径传播,这种情况才会发生。而且在入侵者出现后,需要一定时间才能进行复制。由于用作疫苗的寡肽抗原在组织中的半衰期非常短,没有足够的抗原到达淋巴结并在那里停留足够长的时间以有效诱导免疫反应。通过使用小鼠模型,我们能够证明,通过将疫苗直接注射到模仿淋巴或血行传播的淋巴结或脾脏中,疫苗的效率可以提高一百万倍。通过连续几天给药疫苗,模拟特别危险的病毒复制,“灭活疫苗”的效率可以进一步提高。在这个小鼠模型中收集的证据被应用于一项临床试验。将黑色素瘤特异性灭活疫苗直接注入肿瘤患者的淋巴结。注射持续数天。每两周接种一次加强疫苗。

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