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

Somayeh  Mami; Sajjad  Shekarchian; Alireza Naderi  Sohi; Jafar  Kiani; Masoud  Soleimani; Masoud  Soleimani; Mohammad Hossein  Nicknam

doi:10.18502/ijaai.v25i1.20435

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
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

DOI: https://doi.org/10.18502/ijaai.v25i1.20435

Keywords: Cytomegalovirus; CMV; Immunotoxicity; Lipid Nanoparticles; mRNA-LNP; Safety; Vaccine

Abstract

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.