Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 25 1 2026 01 01 45 57 Somayeh Mami Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Sajjad Shekarchian Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran Alireza Naderi Sohi Department of Stem Cells and Regenerative Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran Jafar Kiani Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran Masoud Soleimani Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Mohammad Hossein Nicknam Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran 2025 04 06 2025 06 06 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. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4409 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4409/2223