疫苗药代动力学研究的现状:载体、ADME以及其在免疫反应中的调节的影响。
Current progress in pharmacokinetic studies of vaccines: Impact of carrier, ADME and its modulation on immune responses.
发表日期:2023 Aug 03
作者:
Saurav Kumar Jha, Mohammad Imran, Laxmi Akhileshwar Jha, Nazeer Hasan, Vijay Kumar Panthi, Keshav Raj Paudel, Waleed H Almalki, Yousuf Mohammed, Prashant Kesharwani
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
对疫苗吸收、分布、代谢和排泄(ADME)的缺乏了解使得生物制药优化困难。这在COVID-19免疫接种活动中得到了证明,因为初始剂量未能提供广泛的感染保护,因此逐渐引入了增强剂量。因此,了解疫苗ADME及其对免疫力有效性的影响可能会在制剂、给药途径和剂量方案方面导致更合理的疫苗设计。本文将介绍关于疫苗药代动力学的信息、输送途径和载体对ADME的影响、纳米颗粒输送载体的利用和效能、剂量水平和剂量方案对疫苗治疗功效的影响、细胞内和内体运输及体内命运、对DNA和mRNA疫苗的展望、新一代测序和数学模型以改善癌症疗法和药理学、以及COVID-19疫苗的毒理学研究。总之,本综述将增强读者对疫苗药代动力学的理解,并介绍可应用于输送载体设计以改善免疫剂的吸收和分布、估算适宜剂量以实现更好的免疫应答和预防毒性的方法。版权所有 © 2023。由爱思唯尔公司出版。
The lack of knowledge about the absorption, distribution, metabolism, and excretion (ADME) of vaccines makes biopharmaceutical optimization difficult. This was shown during the COVID-19 immunization campaign, where gradual booster doses were introduced as the initial dose was not offering broad protection against infection. Thus, understanding vaccine ADME and its effects on immunization effectiveness could result in a more logical vaccine design in terms of formulation, method of administration, and dosing regimens. Herein, we will cover the information available on vaccine pharmacokinetics, impacts of delivery routes and carriers on ADME, utilization and efficiency of nanoparticulate delivery vehicles, impact of dose level and dosing schedule on the therapeutic efficacy of vaccines, intracellular and endosomal trafficking and in vivo fate, perspective on DNA and mRNA vaccines, new generation sequencing and mathematical models to improve cancer vaccination and pharmacology, and the reported toxicological study of COVID-19 vaccines. Altogether, this review will enhance the reader's understanding of the pharmacokinetics of vaccines and methods that can be implied in delivery vehicle design to improve the absorption and distribution of immunizing agents and estimate the appropriate dose to achieve better immunogenic responses and prevent toxicities.Copyright © 2023. Published by Elsevier Inc.