O'Hagan Derek T, Singh Manmohan
Vaccine Research, Chiron Corporation, Emeryville, CA 94608, USA. derek_o'
Expert Rev Vaccines. 2003 Apr;2(2):269-83. doi: 10.1586/14760584.2.2.269.
Adjuvants can be broadly divided into two groups, based on their principal mechanisms of action: vaccine delivery systems and immunostimulatory adjuvants. Vaccine delivery systems are generally particulate (e.g., emulsions, microparticles, immunostimulatory complexes and liposomes) and function mainly to target associated antigens into antigen-presenting cells. However, increasingly, more complex formulations are being developed in which delivery systems are exploited both for the delivery of antigens and also for the delivery of coadministered immunostimulatory adjuvants. The rationale for this approach is to ensure that both antigen and adjuvant are delivered into the same population of antigen-presenting cells. In addition, delivery systems can focus the effect of the adjuvants onto the key cells of the immune system and limit the systemic distribution of the adjuvant, to minimize its potential to induce adverse effects. The formulation and delivery of potent adjuvants in microparticles may allow the development of prophylactic and therapeutic vaccines against cancers and chronic infectious diseases, which are currently poorly controlled. In addition, microparticle formulations may also allow vaccines to be delivered mucosally.
根据其主要作用机制,佐剂可大致分为两类:疫苗递送系统和免疫刺激佐剂。疫苗递送系统通常是颗粒状的(如乳剂、微粒、免疫刺激复合物和脂质体),其主要功能是将相关抗原靶向递送至抗原呈递细胞。然而,越来越多更复杂的制剂正在被开发,其中递送系统既用于递送抗原,也用于递送共同给药的免疫刺激佐剂。这种方法的基本原理是确保抗原和佐剂都被递送至同一群抗原呈递细胞中。此外,递送系统可以将佐剂的作用集中于免疫系统的关键细胞上,并限制佐剂的全身分布,以尽量减少其诱导不良反应的可能性。在微粒中配制和递送强效佐剂可能有助于开发针对癌症和慢性传染病的预防性和治疗性疫苗,目前这些疾病的控制效果不佳。此外,微粒制剂还可能使疫苗能够通过黏膜给药。