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.
Keywords: antigen protection; biomineralization; cryoprotectants; lipid nanoparticles (LNPs); lyophilization; metal−organic coordination polymers; microneedles; polymeric particles; protein denaturation; thermostability; vaccine distribution.