What strategies are used to improve vaccine thermostability?

Vaccine thermostability reduces cold chain requirements, critical for global access. Strategies: 1) Formulation optimization - stabilizing excipients (sugars as glass-formers: trehalose, sucrose; amino acids; surfactants); buffer selection (histidine, phosphate); pH optimization; removal of destabilizing components. 2) Lyophilization - freeze-drying removes water, increasing stability; cycle optimization critical; reconstitution considerations. 3) Spray drying - produces thermostable powder; emerging for vaccines. 4) Controlled Temperature Chain (CTC) - WHO prequalification allowing single excursion to 40C for defined time. 5) Microencapsulation - protect antigens in polymer matrices. 6) Structural engineering - stabilize proteins through mutations; prefusion-stabilized RSV vaccines. 7) Thermostable platforms - some viral vectors and VLPs inherently stable. 8) Sugar glass technology - amorphous sugar matrices preserve antigens. Assessment: accelerated stability studies, Arrhenius kinetics for shelf-life prediction, real-time stability. mRNA vaccines remain challenge due to hydrolysis susceptibility.