Seminars

Today, I present our findings on SARS-CoV-2 mRNA vaccination effects at injection sites. While mRNA vaccines are safe and effective, their local tissue impact under different metabolic conditions remains unclear. We investigated intramuscular vaccination effects using non-human primates and mice under varying diets. Our analyses revealed significant localized injury: mitochondrial dysfunction, inflammation, and structural damage. Transcriptomic profiling showed downregulation of oxidative phosphorylation genes and upregulation of immune/apoptotic pathways. Electron microscopy confirmed disrupted mitochondrial cristae and reduced enzymatic activity. Vaccinated animals exhibited reduced grip strength. Remarkably, ApoE deficiency provided protection, particularly under Western diet. ApoE-deficient mice showed preserved mitochondrial integrity and reduced inflammation despite comparable vaccine expression. These findings reveal critical interactions between metabolic status, lipid metabolism, and vaccine responses, potentially informing personalized vaccination strategies in metabolically diverse populations.