The Role of Biological Sex in Pre-Clinical (Mouse) mRNA Vaccine Studies

In this study, we consider the influence of biological sex-specific immune responses on the assessment of mRNA vaccines in pre-clinical murine studies. Recognising the established disparities in immune function attributed to genetic and hormonal differences between individuals of different biological sexes, we compared the mRNA expression and immune responses in mice of both biological sexes after intramuscular injection with mRNA incorporated within lipid nanoparticles. Regarding mRNA expression, no significant difference in protein (luciferase) expression at the injection site was observed between female and male mice following intramuscular administration; however, we found that female BALB/c mice exhibit significantly greater total IgG responses across the concentration range of mRNA lipid nanoparticles (LNPs) in comparison to their male counterparts. This study not only contributes to the scientific understanding of mRNA vaccine evaluation but also emphasizes the importance of considering biological sex in vaccine study designs during pre-clinical evaluation in murine studies.