Guy Bruno, Burdin Nicolas
Research Department, Aventis Pasteur, Marcy l'Etoile, France.
Therapie. 2005 May-Jun;60(3):235-41. doi: 10.2515/therapie:2005030.
Developing efficient adjuvants for human vaccines, in order to elicit broad and sustained immune responses at systemic or mucosal levels, remains a challenge for the vaccine industry. Conventional approaches in the past have been largely empirical and partially successful. Selection was based on the balance between toxicity and adjuvanticity, first in an animal model, and then in clinical trials. The advent of improved biochemical techniques has allowed for the purification or construction of new and well characterised adjuvants. In addition, recent advances in our understanding of the immune system, most particularly with respect to early proinflammatory signals, have led to the identification of new biological targets for vaccine adjuvants. In particular, one can now choose adjuvants able to selectively induce T helper (Th)-1 and/or Th2 responses, according to the vaccine target and the desired immune response. As our knowledge of the cell types and cytokines interacting in the immune responses increases, so does our understanding of the mode of action of adjuvants, as well as the way in which they produce adverse effects.
开发用于人类疫苗的高效佐剂,以在全身或黏膜水平引发广泛且持久的免疫反应,仍然是疫苗行业面临的一项挑战。过去的传统方法很大程度上是经验性的,且仅取得了部分成功。选择过程基于毒性和佐剂活性之间的平衡,首先在动物模型中进行,然后在临床试验中开展。改进的生化技术的出现使得新型且特性明确的佐剂得以纯化或构建。此外,我们对免疫系统的理解,尤其是关于早期促炎信号方面的最新进展,已促使人们确定了疫苗佐剂的新生物学靶点。特别是,现在可以根据疫苗靶点和期望的免疫反应,选择能够选择性诱导辅助性T细胞(Th)-1和/或Th2反应的佐剂。随着我们对免疫反应中相互作用的细胞类型和细胞因子的了解不断增加,我们对佐剂作用方式以及它们产生不良反应方式的理解也在加深。