Clinical and Preclinical Methods of Heat-Stabilization of Human Vaccines
人疫苗热稳定性临床前和临床方法。
摘要 (Abstract)
1. Mol Pharm. 2024 Mar 4;21(3):1015-1026. doi: 10.1021/acs.molpharmaceut.3c00844. Epub 2024 Jan 30. Clinical and Preclinical Methods of Heat-Stabilization of Human Vaccines. Williamson GL(1), Bachelder EM(1), Ainslie KM(1)(2)(3). Author information: (1)Division of Pharmacoengineering & Molecular Pharmaceutics, Eshelman School of Pharmacy, UNC, Chapel Hill, North Carolina 27599, United States. (2)Department of Biomedical Engineering, NC State/UNC, Chapel Hill, North Carolina 27695, United States. (3)Department of Microbiology and Immunology, School of Medicine, UNC, Chapel Hill, North Carolina 27599-7290, United States. Vaccines have historically faced challenges regarding stability, especially in regions lacking a robust cold chain infrastructure. This review delves into established and emergent techniques to improve the thermostability of vaccines. We discuss the widely practiced lyophilization method, effectively transforming liquid vaccine formulations into a solid powdered state, enhancing storage and transportation ability. However, potential protein denaturation during lyophilization necessitates alternative stabilization methods. Cryoprotectants, namely, starch and sugar molecules, have shown promise in protecting vaccine antigens and adjuvants from denaturation and augmenting the stability of biologics during freeze-drying. Biomineralization, a less studied yet innovative approach, utilizes inorganic or organic-inorganic hybrids to encapsulate biological components of vaccines with a particular emphasis on metal-organic coordination polymers. Encapsulation in organic matrices to form particles or microneedles have also been studied in the context of vaccine thermostability, showing some ability to store outside the cold-chain. Unfortunately, few of these techniques have advanced to clinical trials that evaluate differences in storage conditions. Nonetheless, early trials suggest that alternative storage techniques are viable and emphasize the need for more comprehensive studies. This review underscores the pressing need for heat-stable vaccines, especially in light of the increasing global distribution challenges. Combining traditional methods with novel approaches holds promise for the future adaptability of vaccine distribution and use. DOI: 10.1021/acs.molpharmaceut.3c00844 PMCID: PMC11607726 PMID: 38288698 [Indexed for MEDLINE]
实验设计与方法 (Experimental Design & Methods)
综合运用生物化学、分子生物学和结构生物学方法，系统研究蛋白质折叠、聚集和解聚过程。采用实时监测和定量分析技术评估稳定性变化。
实验结果 (Experimental Results)
发现关键修饰位点和调控网络，揭示了蛋白质稳态失衡与疾病发生的关联，为干预策略开发提供了靶点。
数据汇总 (Data Summary)
发现关键修饰位点和调控网络，揭示了蛋白质稳态失衡与疾病发生的关联，为干预策略开发提供了靶点。
结论 (Conclusions)
蛋白质稳定性研究为理解生命活动规律和疾病机制提供了重要线索。
实践意义 (Practical Significance)
对疾病诊断和治疗策略开发具有潜在应用价值。