Enhanced subchronic cardiac stress of high doses of a novel SARS-CoV-2 mRNA vaccine candidate in streptozotocin-induced diabetic mice.

Although mRNA vaccines have been pivotal in combating the COVID-19 pandemic, research on their side effects remains limited. Adverse effects can vary considerably, including cardiac injury, and individuals with diabetes may experience broader reactions. This study compared vehicle (Veh) and streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) mouse models following administration of the novel SARS-CoV-2 mRNA vaccine candidate CUK3-1/LNP128 to evaluate its toxicity profile and assess potential adverse effects in the presence of underlying disease. Flow cytometry, enzyme-linked immunosorbent assay, and enzyme-linked immunospot analyses showed comparable activation of Th1 and cytotoxic T cell responses in both groups. Hematological analysis revealed increased neutrophil and decreased lymphocyte counts after vaccination, with no significant differences between groups. Veh and STZ mice exhibited elevated c-Troponin-I levels, indicative of myocardial injury, with a greater increase observed in STZ mice. Aspartate aminotransferase and lactate dehydrogenase levels were also higher in STZ mice, suggesting enhanced cardiotoxic potential. Notably, in parallel with elevated malondialdehyde levels and 4-hydroxynonenal immunoreactivity, cardiac protein levels of COX2, NF-κB, TNF-α, IL-1β, IL-6, and IL-12a were significantly higher in vaccinated STZ mice. These findings indicate that CUK3-1/LNP128 may exacerbate cardiotoxicity in T1DM, underscoring the need for careful monitoring of adverse effects in these patients.