Cunningham Anthony L, Garçon Nathalie, Leo Oberdan, Friedland Leonard R, Strugnell Richard, Laupèze Béatrice, Doherty Mark, Stern Peter
Westmead Institute, The Centre for Virus Research, 176 Hawkesbury Road, NSW 2145, Australia.
Bioaster, 321 Avenue Jean Jaurès, 69007 Lyon, France.
Vaccine. 2016 Dec 20;34(52):6655-6664. doi: 10.1016/j.vaccine.2016.10.016. Epub 2016 Oct 18.
In the 21st century, an array of microbiological and molecular allow antigens for new vaccines to be specifically identified, designed, produced and delivered with the aim of optimising the induction of a protective immune response against a well-defined immunogen. New knowledge about the functioning of the immune system and host pathogen interactions has stimulated the rational design of vaccines. The design toolbox includes vaccines made from whole pathogens, protein subunits, polysaccharides, pathogen-like particles, use of viral/bacterial vectors, plus adjuvants and conjugation technology to increase and broaden the immune response. Processes such as recombinant DNA technology can simplify the complexity of manufacturing and facilitate consistent production of large quantities of antigen. Any new vaccine development is greatly enhanced by, and requires integration of information concerning: 1. Pathogen life-cycle & epidemiology. Knowledge of pathogen structure, route of entry, interaction with cellular receptors, subsequent replication sites and disease-causing mechanisms are all important to identify antigens suitable for disease prevention. The demographics of infection, specific risk groups and age-specific infection rates determine which population to immunise, and at what age. 2. Immune control & escape. Interactions between the host and pathogen are explored, with determination of the relative importance of antibodies, T-cells of different types and innate immunity, immune escape strategies during infection, and possible immune correlates of protection. This information guides identification and selection of antigen and the specific immune response required for protection. 3. Antigen selection & vaccine formulation. The selected antigen is formulated to remain suitably immunogenic and stable over time, induce an immune response that is likely to be protective, plus be amenable to eventual scale-up to commercial production. 4. Vaccine preclinical & clinical testing. The candidate vaccine must be tested for immunogenicity, safety and efficacy in preclinical and appropriately designed clinical trials. This review considers these processes using examples of differing pathogenic challenges, including human papillomavirus, malaria, and ebola.
在21世纪，一系列微生物学和分子学方法使新型疫苗的抗原能够被特异性识别、设计、生产和递送，目的是优化针对明确免疫原的保护性免疫反应的诱导。关于免疫系统功能和宿主-病原体相互作用的新知识推动了疫苗的合理设计。设计工具箱包括由完整病原体、蛋白质亚基、多糖、病原体样颗粒制成的疫苗，病毒/细菌载体的使用，以及用于增强和扩大免疫反应的佐剂和偶联技术。重组DNA技术等方法可以简化生产的复杂性，并有助于大量一致地生产抗原。任何新疫苗的开发都因整合以下信息而得到极大加强，并且需要这些信息的整合：1. 病原体生命周期和流行病学。了解病原体结构、进入途径、与细胞受体的相互作用、随后的复制位点和致病机制对于识别适合疾病预防的抗原都很重要。感染的人口统计学、特定风险群体和特定年龄的感染率决定了要免疫哪些人群以及在什么年龄进行免疫。2. 免疫控制与逃逸。探索宿主与病原体之间的相互作用，确定不同类型的抗体、T细胞和先天免疫的相对重要性、感染期间的免疫逃逸策略以及可能的保护免疫相关因素。这些信息指导抗原的识别和选择以及保护所需的确切免疫反应。3. 抗原选择与疫苗配方。所选抗原经过配方设计，以使其在一段时间内保持适当的免疫原性和稳定性，诱导可能具有保护性的免疫反应，并且适合最终扩大到商业生产规模。4. 疫苗临床前和临床试验。候选疫苗必须在临床前和经过适当设计的临床试验中进行免疫原性、安全性和有效性测试。本综述通过不同致病挑战的例子，包括人乳头瘤病毒、疟疾和埃博拉病毒，来探讨这些过程。
