Jennings R, Simms J R, Heath A W
Division of Molecular and Genetic Medicine, University of Sheffield Medical School, U.K.
Dev Biol Stand. 1998;92:19-28.
Of the vaccines against viral diseases of man currently available, several are less than satisfactory, and the present surge of interest in improving such vaccines, and in developing new vaccines against viral diseases as yet unchallenged, has led to major developments in three areas. The capacity to identify the nature and form of antigenic epitopes in proteins allows the specific design of molecular entities to promote relevant and protective immune responses. Such entities, although ideal in terms of specificity and purity, may not achieve their goals through failure to reach relevant cells of the immune system due to simple dilution, elimination by host enzymes or lack of specific targeting. Concomitant with the above there has been development of a plethora of adjuvants aimed at enhancing immune responses to these 'new' immunogens, paralleled by an almost equally rapid increase in understanding the complex nature of the immune response, particularly with respect to antigen processing, the nature and role of cytokines and the importance of T-cell subsets in infection. These developments allow exploration of matching the properties and mechanistic action of a given adjuvant to a defined immune response. Adjuvants can be grouped according to their physical characteristics and mode of action. They include particulate adjuvants, oil and emulsifier-based adjuvants, those providing controlled antigen delivery, adjuvants based on specific targeting of antigen, and gel-type adjuvants. They may act non-specifically in promoting an immune response to an antigen through depot formation, or very specifically as in a "delivery system" where an antigen is linked to a cellular protein, targeted to a specific cell receptor. As adjuvant technology develops it is becoming increasingly clear that these differing approaches may be combined, and an adjuvant/delivery system designed, to provide slow release of a targeted antigen. The role of adjuvants in modern viral vaccine technology and their influence on the immune system are the subject of this review.
在目前可获得的用于预防人类病毒性疾病的疫苗中，有几种并不尽如人意。当前，人们对改进此类疫苗以及研发针对尚未受到挑战的病毒性疾病的新疫苗兴趣高涨，这在三个领域带来了重大进展。确定蛋白质中抗原表位的性质和形式的能力，使得能够对分子实体进行特定设计，以促进相关的保护性免疫反应。这类实体尽管在特异性和纯度方面堪称理想，但可能由于简单稀释、被宿主酶消除或缺乏特异性靶向作用而无法到达免疫系统的相关细胞，从而无法实现其目标。与此同时，大量旨在增强对这些“新型”免疫原免疫反应的佐剂得以开发，与此同时，人们对免疫反应复杂性质的理解也几乎同样迅速地增加，特别是在抗原加工、细胞因子的性质和作用以及T细胞亚群在感染中的重要性方面。这些进展使得人们能够探索将特定佐剂的特性和作用机制与特定的免疫反应相匹配。佐剂可根据其物理特性和作用方式进行分类。它们包括颗粒佐剂、基于油和乳化剂的佐剂、提供可控抗原递送的佐剂、基于抗原特异性靶向的佐剂以及凝胶型佐剂。它们可能通过形成储库非特异性地促进对抗原的免疫反应，或者像在“递送系统”中那样非常特异性地发挥作用，即抗原与细胞蛋白相连，靶向特定的细胞受体。随着佐剂技术的发展，越来越明显的是，这些不同的方法可以结合起来，设计出一种佐剂/递送系统，以实现靶向抗原的缓慢释放。佐剂在现代病毒疫苗技术中的作用及其对免疫系统的影响是本综述的主题。
