Non-clinical safety evaluation of novel vaccines and adjuvants: new products, new strategies
Non-clinical safety evaluation of novel vaccines and adjuvants: new products, new strategies
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DOI：
10.1016/j.vaccine.2004.11.072
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发表时间：
2005-05-02
期刊：
影响因子：
5.5
通讯作者：
Dougan, G
中科院分区：
文献类型：
--
作者：
Brennan, FR;Dougan, G
分子生物学和生物技术的进步，加上对疾病过程和保护性免疫机制的理解的增加，促进了利用重组蛋白、裸DNA、活载体、遗传修饰毒素和完整树突状细胞和肿瘤细胞的新的合理设计的疫苗的开发，用于预防和治疗广泛的适应症。这些新的疫苗技术加上新的佐剂、递送系统、制剂、给药途径和方案，在证明产品安全性和有效性以支持临床试验方面提出了许多独特而困难的挑战。本文旨在回顾这些新的疫苗和佐剂技术，并强调与它们潜在相关的关键安全性问题。介绍了在现行法规框架内通过评估全身和局部毒性、生物分布和持久性、免疫原性和免疫毒性、生殖毒理学、安全药理学和遗传毒性来证明疫苗安全性的方法。(c)2005爱思唯尔有限公司保留所有权利。
Advances in molecular biology and biotechnology, coupled with an increased understanding of disease processes and mechanisms of protective immunity have facilitated the development of new rationally-designed vaccines utilising recombinant proteins, naked DNA, live vectors, genetically-modified toxins and whole dendritic and tumour cells for both prophylaxis and therapy of a wide range of indications. These new vaccine technologies coupled with novel adjuvants, delivery systems, formulations, dosing routes and regimes present many unique and difficult challenges in demonstrating product safety and efficacy to support clinical testing. This paper aims to review these novel vaccine and adjuvant technologies and to highlight the key safety issues potentially associated with them. Approaches taken to demonstrate vaccine safety by assessing systemic and local toxicity, biodistribution and persistence, immunogenicity and immunotoxicity, reproductive toxicology, safety pharmacology and genotoxicity within the current regulatory framework are presented. (c) 2005 Elsevier Ltd. All rights reserved.