In vitro Safety and Immunotoxicity Assessment of a Novel mRNA-LNP Vaccine against Cytomegalovirus: Insights into Safety and Immunomodulatory Profiles.

Predominantly a widespread beta herpesvirus, human cytomegalovirus (HCMV) triggers lifelong latent infection in most of the people, and HCMV vaccine development has been designated a high public health priority. In the current study, the in vitro safety profile and potential immunotoxic effects of a novel messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccine designed against human cytomegalovirus (HCMV) were assessed. The aim was to measure inflammation, allergic reactions, complement activation, cytotoxicity, and hemolytic effects of the mRNA-LNP vaccine. Proinflammatory cytokine secretion, evident in human peripheral blood mononuclear cells (hPBMCs) treated with unmodified mRNA-LNP, was markedly attenuated by incorporating modified nucleotides. The vaccine appeared incapable of sparking allergic cytokine production or complement activation. Cell viability assays indicated no pronounced cytotoxicity, and hemolysis assays showed no notable hemolytic activity. The findings suggest that the modified mRNA-LNP vaccine exhibits a promising in vitro safety profile, supporting further development of this vaccine candidate.