Wahome Newton, Hickey John M, Volkin David B, Middaugh C Russell
Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, 2095 Constant Ave, Lawrence, KS, 66047, USA.
Methods Mol Biol. 2016;1404:393-421. doi: 10.1007/978-1-4939-3389-1_27.
A critical element of vaccine formulation studies is the identification of chemical and physical degradation pathways that compromise structural integrity, and which may in turn affect the clinical safety and efficacy, of macromolecular antigens. Formulation development helps optimize and maintain the long-term storage stability and viability of vaccine antigens in pharmaceutically relevant dosage forms. The protocols presented in this manuscript highlight the use of accelerated stability studies for the formulation of influenza vaccine candidates including virus-like particles (VLP) and particle forming hemagglutinin (HA) antigens. Three case studies, each targeting a different facet of preclinical vaccine formulation development, are reviewed: (1) excipient screening experiments to mitigate VLP physical degradation, (2) methods for monitoring a specific chemical perturbation of the recombinant HA antigen and elucidating its effect on in vitro potency, and (3) maintaining HA conformational stability in the presence of freeze-thaw and freeze-drying stresses.
疫苗制剂研究的一个关键要素是识别那些会损害大分子抗原结构完整性、进而可能影响其临床安全性和有效性的化学和物理降解途径。制剂研发有助于优化并维持疫苗抗原在药学相关剂型中的长期储存稳定性和活性。本手稿中介绍的方案突出了加速稳定性研究在流感候选疫苗制剂研发中的应用，这些候选疫苗包括病毒样颗粒（VLP）和颗粒形成血凝素（HA）抗原。本文回顾了三个案例研究，每个案例针对临床前疫苗制剂研发的一个不同方面：（1）减轻VLP物理降解的辅料筛选实验，（2）监测重组HA抗原特定化学扰动并阐明其对体外效力影响的方法，以及（3）在冻融和冻干应激条件下维持HA的构象稳定性。
