Mrsny R J
J Drug Target. 1998;6(4):243-9. doi: 10.3109/10611869808996832.
Vaccines have provided generations of individuals with protection against a number of devastating childhood diseases and, in the case of smallpox, have eradicated the disease. Arguably, this preventive approach to health care may have saved more lives than all other therapeutic approaches combined. Being commonly composed of killed-whole or live-attenuated organisms, successful vaccines have been capable of not only presenting crucial epitopes required for protective immunity but also components which stimulate the immune system provide a response of sufficient intensity to provide sustained protection. It is unlikely, however, that these same vaccines would be approved in today's regulatory climate where manufacturers must validate a highly reproducible manufacturing process and demonstrate the exact composition of the final product through stringent quality control (Gupta, 1997). Therefore, companies involved in the identification of new vaccines and their production appear to be moving away from the ill-defined and poorly-controlled immunogens of the past. Instead, they have started employing recombinant biotechnology to produce large quantities of specific antigens with the hope that these antigens will provide protective immunity. Antigen identification can take years of investigation. This process could be speeded up, however, by understanding the mechanisms which pathogens such as viruses and bacteria use to infect the host, their replication cycle and the steps they frequently take to evade the host immune system. Such a rational approach to immunogen design results in what has been termed an "intelligent" vaccine (Plough, 1998). "Intelligent" vaccines will likely be completely composed of artificial or synthetically derived products using recombinant and cell culture technologies and hopefully will allow manufacturers to develop products with the desired efficacy and safety profiles required by regulatory authorities. But unlike the complex and ill-defined immunogens of the past, these specific antigens are frequently poorly antigenic by themselves when compared to whole organisms. Co-delivery with a variety of agents, known as adjuvants, has been shown to increase the antigenicity of these poorly antigenic immunogens. In this editorial, I review the recent patent literature as it pertains to targeting of specific antigens and the role played by various classes of adjuvants to enable or enhance such targeted deliveries.
疫苗已为几代人提供了针对多种毁灭性儿童疾病的保护，就天花而言，已根除了该疾病。可以说，这种预防性医疗保健方法挽救的生命可能比所有其他治疗方法加起来还要多。成功的疫苗通常由灭活的全病原体或减毒活病原体组成，不仅能够呈现保护性免疫所需的关键表位，还能包含刺激免疫系统并引发足够强度反应以提供持续保护的成分。然而，在如今的监管环境下，这些疫苗不太可能获得批准，因为制造商必须验证高度可重复的生产工艺，并通过严格的质量控制来证明最终产品的确切成分（古普塔，1997年）。因此，参与新型疫苗研发和生产的公司似乎正在摒弃过去那些定义不明确且控制不佳的免疫原。相反，他们开始采用重组生物技术大量生产特定抗原，希望这些抗原能提供保护性免疫。抗原鉴定可能需要数年的研究。然而，通过了解病毒和细菌等病原体用于感染宿主的机制、它们的复制周期以及它们逃避宿主免疫系统的常见步骤，这个过程可以加快。这种合理的免疫原设计方法产生了所谓的“智能”疫苗（普劳，1998年）。“智能”疫苗可能完全由使用重组和细胞培养技术的人工或合成衍生产品组成，有望使制造商开发出监管机构要求的具有所需疗效和安全性的产品。但与过去复杂且定义不明确的免疫原不同，这些特定抗原与全病原体相比，自身往往抗原性较差。与多种被称为佐剂的物质共同递送，已被证明可以增加这些低抗原性免疫原的抗原性。在这篇社论中，我回顾了近期与特定抗原靶向以及各类佐剂在实现或增强此类靶向递送中所起作用相关的专利文献。
