Vaccination-induced Myocarditis in Mice Predisposed to Autoimmune Disease

This chapter focused on Vaccination-induced myocarditis in mice predisposed to autoimmune disease. Nonobese diabetic (NOD)/ShiLtJ mice, like biobreeding rats, are used as an animal model for type 1 diabetes. Insulitis, a leukocytic infiltration of the pancreatic islets, causes diabetes in NOD mice. Nonfasting hyperglycemia and moderate glycosuria are linked to the onset of diabetes. Previous studies have looked into the potential contribution of decreased nuclear factor-B1 (NF-B1) (also known as p50) expression to the spontaneous development of type 1 diabetes in NOD/ShiLtJ mice. To investigate the involvement of NF-kB1 in the development of autoimmune diseases, we created NOD-NF-kB1 deficient mice. To understand the risks and consequences of myocarditis following vaccinations with many vaccines, including COVID-19, we examined an experimental system using genetically modified small animals. Because of the polygenetic nature of autoimmune diseases, autoimmune disease is difficult to spontaneously induce in genetically modified mice. These considerations led to the development of NOD mice with variable NF-B1 expression. Surprisingly, it was discovered that the majority of NOD Nfb1 homozygote mice died by the eighth week of life from severe myocarditis. Male mice had a somewhat higher incidence of spontaneous myocarditis than female mice. Furthermore, insulitis was observed in all NOD Nfkb1 heterozygote mice as early as 4 months of age. Additionally, in NOD Nfkb1 heterozygote mice, myocarditis with an increase in cTnT levels due to influenza or hepatitis B virus vaccination was observed with no significant gender difference. However, myocarditis was not observed with the two types of human papillomavirus vaccination. Immunological tests and histological analyses showed that vaccination could cause myocarditis in mice with genetic modifications. In this study, we report that NOD Nfkb1 heterozygote mice can be used for investigating the risk of myocarditis development after vaccination. Our findings will provide new insights into the risk factors involved in the development of cardiovascular disorders such as myocarditis after vaccination, as well as the development of clinical treatments for these disorders.