de Veer Mike, Meeusen Els
Biotechnology Research Laboratories, School of Biomedical Sciences, Monash University, Melbourne, Victoria 3800, Australia.
Discov Med. 2011 Sep;12(64):195-204.
Since the first mass vaccination against smallpox and its eventual eradication, many more vaccines have been developed based on advances in bacteriology and virology and the use of attenuated live or killed whole pathogens. Immunological discoveries have allowed the development of more refined anti-toxin and conjugate vaccines, while biotechnology provided the tools for rationally designed, genetically engineered vaccines. Many challenges remain in developing safer and more effective vaccines against the more complex diseases such as tuberculosis and HIV-AIDS, and for the rapid protection against newly emerging pathogens or pathogen strains. These vaccines are likely to require the isolation of the "protective" antigenic molecules from the whole pathogen, as well as ways to deliver these to induce effective immune responses with minimal side effects. It has long been recognized that most antigens require the addition of an "adjuvant," an ill-defined substance that non-specifically triggers the innate immune system and boosts an immune response, with aluminum-based adjuvants the most commonly used in most present vaccines. Recent immunological breakthroughs have uncovered that the innate immune system has a much higher degree of complexity than previously thought and can be activated along a wide range of different pathways, depending on the engagement of different innate immune receptors. This in turn determines the type of immune response that will be generated against the vaccine antigens or pathogens. Harvesting the complexity and exquisite specificity of this innate immune system has inspired a new direction in vaccine research, towards the generation of novel adjuvant formulations, tailored to induce defined immune responses effective against specific pathogens. This review gives a brief overview of vaccine development and summarizes different aspects of adjuvant formulation that may influence their activity and specificity.
自首次大规模接种天花疫苗并最终实现天花根除以来，基于细菌学和病毒学的进展以及减毒活病原体或灭活全病原体的使用，又研发出了更多疫苗。免疫学的发现推动了更精制的抗毒素疫苗和结合疫苗的发展，而生物技术则为合理设计的基因工程疫苗提供了工具。在研发针对结核病和艾滋病毒/艾滋病等更复杂疾病的更安全、更有效的疫苗，以及针对新出现的病原体或病原体菌株进行快速防护方面，仍存在许多挑战。这些疫苗可能需要从全病原体中分离出“保护性”抗原分子，以及将这些分子递送至体内以诱导有效免疫反应且副作用最小的方法。长期以来人们就认识到，大多数抗原需要添加一种“佐剂”，一种作用尚不明确的物质，它能非特异性地触发先天免疫系统并增强免疫反应，铝基佐剂是目前大多数疫苗中最常用的佐剂。最近的免疫学突破揭示，先天免疫系统的复杂性比之前认为的要高得多，并且可以根据不同先天免疫受体的激活沿着多种不同途径被激活。这反过来又决定了针对疫苗抗原或病原体产生的免疫反应类型。利用这种先天免疫系统的复杂性和精妙特异性，激发了疫苗研究的一个新方向，即研发新型佐剂配方，以诱导针对特定病原体有效的特定免疫反应。本综述简要概述了疫苗的发展，并总结了佐剂配方可能影响其活性和特异性的不同方面。
