Effects of vaccines targeting interleukin‐1 receptor, type I on atrial and ventricular function after myocardial infarction

BACKGROUND AND PURPOSE: The strong relationship between myocardial infarction (MI) and inflammation has been supported by numerous observations; targeting inflammatory signalling pathways represents a crucial approach to rescue cardiac function after MI. Our team has designed and developed therapeutic vaccines, ILRQβ-007 and ILRQβ-008, which target interleukin-1 receptor, type I (IL-1R1). The aim of this study is to investigate the effect of the vaccines on short-term and long-term MI animal models. EXPERIMENTAL APPROACH: The ILRQβ-007 and ILRQβ-008 vaccines were prepared and then used to immunize C57BL/6J (C57) mice with MI and observed their effects at 7 and 28 days, respectively. Cardiac ultrasound and histological staining were used to assess cardiac function and remodelling after MI in C57 mice. Flow cytometry and molecular biology tests were used to evaluate the systemic inflammatory infiltrate. While transesophageal catheter pacing was used to assess susceptibility to atrial fibrillation in mice. RESULTS: The vaccines produced high titres of antibodies and reduced IL-1R1 expression levels in the heart after MI. They significantly reduced myocardial infarct size and systemic inflammation following short-term MI, as well as protecting cardiac function and reducing cardiac fibrosis following long-term MI. Moreover, the susceptibility to atrial fibrillation was reduced in both the short and long-term models. Further, the vaccines improved mitochondrial dynamics and thus maintained mitochondrial homeostasis protecting the heart. CONCLUSION AND IMPLICATIONS: This study demonstrates that vaccines targeting IL-1R1 can be applied to the prevention and treatment of MI, providing a new direction for MI research.