Developability assessments with four mRNA-LNP vaccine formulations comparing mouse immunogenicity, structural attributes, and stability profiles (Dataset)
Elbaz, Nancy M. Vander Straten, Aurelien Ingham, David J. Neuenswander, Sarah A.
Elbaz, Nancy M.
Vander Straten, Aurelien
Ingham, David J.
Neuenswander, Sarah A.
Abstract
To facilitate identifying new mRNA-LNP vaccine formulations with improved pharmaceutical properties while maintaining comparable biological potency, a standardized developability assessment workflow was established to rank-order the stability profiles of multiple candidates. As proof-of-concept, three early-development, experimental mRNA-LNPs with varying lipid composition were benchmarked against a Spikevax® mimic via mouse immunogenicity studies and various stability studies using a “routine analytical toolbox” monitoring the (1) chemical integrity of the mRNA and lipid components, (2) structural integrity of the assembled nanoparticles, and (3) functionality of the mRNA-LNPs (i.e., cell-based transfection assays). Although the four mRNA-LNPs had overall similar in vivo performance (using mRNA encoding glycoprotein G rabies antigen) as measured by neutralizing antibody titers in mice, their in vitro stability profiles in a common liquid formulation buffer varied substantially (using mRNA encoding luciferase). Varying losses of functionality (i.e., decreasing luciferase expression) were observed upon exposure to different environmental stresses, which correlated with distinct physicochemical mechanisms including mRNA degradation at elevated temperatures and disruption of LNP structure upon agitation and freeze-thaw. Heat-map analysis of the analytical results enabled a rank-ordering of the overall stability profiles of the four mRNA-LNPs. Interestingly, further characterization by two higher-resolution analytical techniques (cryo-EM and ¹H-NMR) identified structural attributes of the four mRNA-LNPs (i.e., bleb formulation and lipid surface topology, respectively) at time zero that correlated with their observed stability profiles. Results are discussed in the context of how adding multiple stability assessments to a standardized mRNA-LNP developability platform can accelerate identification and development of mRNA-LNP vaccine candidates with optimized biological and pharmaceutical properties
Description
This is the dataset for the article Developability assessments with four mRNA-LNP vaccine formulations comparing mouse immunogenicity, structural attributes, and stability profiles, published in 2026 in the Journal of Pharmaceutical Sciences (Elsevier). The DOI for the published article is https://doi.org/10.1016/j.xphs.2026.104199
Date
2025
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University of Kansas, Department of Pharmaceutical Chemistry
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Keywords
mRNA LNPs, Vaccine, Cationic lipids, Developability, Stability, Formulation, Immunogenicity