A novel vaccine targeting β1-adrenergic receptor

Abstract

Beta-blockers are widely used in the treatment of hypertension, heart failure and ischemic heart disease. However, unstandardized medication results in diverse clinical outcomes in patients. The main causes are unattained optimal doses, insufficient follow-up and patients' poor adherence. To improve the medication inadequacy, our team developed a novel therapeutic vaccine targeting β1-adrenergic receptor (β1-AR). The β1-AR vaccine named ABRQβ-006 was prepared by chemical conjugation of a screened β1-AR peptide with Qβ virus like particle (VLP). The antihypertensive, anti-remodeling and cardio-protective effects of β1-AR vaccine were evaluated in different animal models. The ABRQβ-006 vaccine was immunogenic that induced high titers of antibodies against β1-AR epitope peptide. In the NG-nitro-L-arginine methyl ester (L-NAME) + Sprague Dawley (SD) hypertension model, ABRQβ-006 lowered systolic blood pressure about 10 mmHg and attenuated vascular remodeling, myocardial hypertrophy and perivascular fibrosis. In the pressure-overload transverse aortic constriction (TAC) model, ABRQβ-006 significantly improved cardiac function, decreased myocardial hypertrophy, perivascular fibrosis and vascular remodeling. In the myocardial infarction (MI) model, ABRQβ-006 effectively improved cardiac remodeling, reduced cardiac fibrosis and inflammatory infiltration, which was superior to metoprolol. Moreover, no significant immune-mediated damage was observed in immunized animals. The ABRQβ-006 vaccine targeting β1-AR showed the effects on hypertension and heart rate control, myocardial remodeling inhibition and cardiac function protection. These effects could be differentiated in different types of diseases with diverse pathogenesis. ABRQβ-006 could be a novel and promising method for the treatment of hypertension and heart failure with different etiologies.

Keywords: Cardiac Remodeling; Heart Failure; Hypertension; Therapeutic Vaccine; β1-AR.