The novel vaccines targeting interleukin-1 receptor type I

Abstract

Objective: There is mounting evidence indicating that atherosclerosis represents a persistent inflammatory process, characterized by the presence of inflammation at various stages of the disease. Interleukin-1 (IL-1) precisely triggers inflammatory signaling pathways by binding to interleukin-1 receptor type I (IL-1R1). Inhibition of this signaling pathway contributes to the prevention of atherosclerosis and myocardial infarction. The objective of this research is to develop therapeutic vaccines targeting IL-1R1 as a preventive measure against atherosclerosis and myocardial infarction.

Methods: ILRQβ-007 and ILRQβ-008 vaccines were screened, prepared and then used to immunize high-fat-diet fed ApoE^-/- mice and C57BL/6J mice following myocardial infarction. Progression of atherosclerosis in ApoE^-/- mice was assessed primarily by oil-red staining of the entire aorta and aortic root, as well as by detecting the extent of macrophage infiltration. The post-infarction cardiac function in C57BL/6J mice were evaluated using cardiac ultrasound and histological staining.

Results: ILRQβ-007 and ILRQβ-008 vaccines stimulated animals to produce high titers of antibodies that effectively inhibited the binding of interleukin-1β and interleukin-1α to IL-1R1. Both vaccines effectively reduced atherosclerotic plaque area, promoted plaque stabilization, decreased macrophage infiltration in plaques and influenced macrophage polarization, as well as decreasing levels of inflammatory factors in the aorta, serum, and ependymal fat in ApoE^-/- mice. Furthermore, these vaccines dramatically improved cardiac function and macrophage infiltration in C57BL/6J mice following myocardial infarction. Notably, no significant immune-mediated damage was observed in immunized animals.

Conclusion: The vaccines targeting the IL-1R1 would be a novel and promising treatment for the atherosclerosis and myocardial infarction.

Keywords: Anti-inflammation; Atherosclerosis; IL-1 receptor; Macrophage; Therapeutic Vaccine.