Evaluation of the stability of the mRNA-based COVID-19 vaccine developed at Bio-Manguinhos

Introduction: COVID-19 has had an impact on global public health, stimulating scientific progress and investment in the production and development of vaccines, especially mRNA vaccines.These vaccines are a special type of immunobiological, whose quality is highly sensitive to temperature, requiring an endto-end cold supply chain, from manufacturing, transportation to warehouses and health facilities.In this context, understanding stability and optimizing the production process could make transport and storage at ambient or refrigerated temperatures feasible throughout the vaccine supply chain. Objectives:The objective of this work was to evaluate the stability of a formulation to choose long-term storage conditions for the COVID-19 mRNA vaccine developed at Bio-Manguinhos. Methodology:The formulation of lipid nanoparticles (LNPs) was prepared in three different batches, containing an ionizable lipid, an auxiliary phospholipid, cholesterol, and a PEG-anchored lipid, loaded with non-replicative mRNA.The formulation was stored at three different temperatures (2 -8 C, -30 C and -80 C) and two concentrations of a cryoprotectant used in vaccines (sucrose -0% and 10%) for 60 days.It was checked how these differences might influence the critical quality attributes, CQAs (particle size, PDI, zeta potential, and encapsulation efficiency). Results:The results of the characterizations showed that the LNPs could be kept at 2 -8 C, during the period studied, without significant alteration of the CQAs, especially in the presence of 10% sucrose.At -30 C, in the presence of 10% sucrose, stability was maintained over this period.However, the LNPs stored at -80 C showed CQA values that differed from the recommended parameters, indicating that this would not be a suitable temperature for storing the vaccine. Conclusion:The results of this project aim to study the stability of mRNA-based COVID-19 vaccine formulation of Bio-Manguinhos allowing storage and transportation at temperatures that are accessible in all parts of Brazil contributing to Brazil's autonomy in the manufacture of these vaccines.