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疫苗药代动力学研究的全面综述:传递途径、载体及其对免疫反应的调节作用的影响。

A Comprehensive review on Pharmacokinetic Studies of Vaccines: Impact of delivery route, carrier-and its modulation on immune response.

机构信息

Department of Biomedicine, Health & Life Convergence Sciences, Mokpo National University, Muan-gun, Jeonnam, 58554, Republic of Korea; Department of Biological Sciences and Bioengineering (BSBE), Indian Institute of Technology, Kanpur, 208016, Uttar Pradesh, India.

Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, 4102, Australia.

出版信息

Environ Res. 2023 Nov 1;236(Pt 2):116823. doi: 10.1016/j.envres.2023.116823. Epub 2023 Aug 3.

Abstract

The lack of knowledge about the absorption, distribution, metabolism, and excretion (ADME) of vaccines makes former biopharmaceutical optimization difficult. This was shown during the COVID-19 immunization campaign, where gradual booster doses were introduced.. 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.

摘要

疫苗的吸收、分布、代谢和排泄(ADME)知识的缺乏使得以前的生物制药优化变得困难。这在 COVID-19 免疫接种运动中得到了体现,其中逐渐引入了加强剂量。因此,了解疫苗的 ADME 及其对免疫效果的影响,可以在配方、给药途径和剂量方案方面实现更合理的疫苗设计。在此,我们将介绍有关疫苗药代动力学的信息,包括给药途径和载体对 ADME 的影响、纳米颗粒递送载体的利用和效率、剂量水平和给药方案对疫苗治疗效果的影响、细胞内和内体运输以及体内命运、DNA 和 mRNA 疫苗的展望、新一代测序和数学模型以改善癌症疫苗接种和药理学,以及 COVID-19 疫苗的毒理学研究报告。总的来说,这篇综述将提高读者对疫苗药代动力学的理解,并了解可应用于递送载体设计中的方法,以改善免疫剂的吸收和分布,并估计适当的剂量以实现更好的免疫应答并预防毒性。

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