International journal of pharmaceuticsNov 24, 2025

New freeze-drying methods for mRNA vaccines against infectious diseases

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Freeze-drying is reviewed as a strategy to improve mRNA vaccine stability by reducing moisture-driven mRNA degradation.

Evidence

This was a review of freeze-drying technologies for infectious-disease mRNA vaccines, covering lyophilization stages, formulation composition, process parameters, manufacturing environment, and optimization strategies.

Caveat

The abstract presents process guidance rather than new comparative vaccine performance data, and it emphasizes that freeze-drying stresses and many process variables remain key challenges.

Simplified

Currently, the storage and transportation of mRNA vaccines typically rely on ultra-low temperature conditions. To improve their stability and extend shelf life, recent studies have been devoted to converting liquid formulations into solid forms using drying technology. Among them, freeze-drying (lyophilization) is an effective strategy that freezes samples and removes moisture through primary (sublimation) and secondary (desorption) drying stages, maximally preserving the structural integrity and biological activity of mRNA vaccines. The significant reduction in moisture content effectively inhibits the rate of hydrolysis of mRNA, which is considered the primary factor contributing to the instability of mRNA vaccines. However, the freeze-drying process itself and its accompanying stresses pose key challenges, involving many critical variables closely related to formulation composition, process parameters, and manufacturing environment. This paper systematically reviews the application of different freeze-drying technologies in mRNA vaccines and the optimization strategies of lyophilized mRNA vaccines, aiming to provide theoretical foundation and guidance for optimizing freeze-drying processes, enhancing vaccine stability and expanding their application scope.