Vaccination in Atherosclerosis

Abstract

Atherosclerosis is the major underlying pathology of cardiovascular diseases that together are the leading cause of death worldwide. The formation of atherosclerotic plaques is driven by chronic vascular inflammation. Although several risk factors have been identified and significant progress in disease prevention and treatment has been made, no therapeutic agents targeting inflammation are clinically available. Recent clinical trials established the potential of anti-inflammatory therapies as a treatment of atherosclerosis. However, adverse impacts on host defense have raised safety concerns about these therapies. Scientific evidence during the past 40 years implicated an adaptive immune response against plaque-associated autoantigens in atherogenesis. Preclinical data have underscored the protective potential of immunization against such targets precisely and without the impairment of host defense. In this review, we discuss the current vaccination strategies against atherosclerosis, supposed mechanisms of action, therapeutic potential, and the challenges that must be overcome in translating this idea into clinical practice.

Keywords: antibodies; antigen-specific; apolipoprotein B (ApoB); atherosclerosis; immunization; low-density lipoprotein (LDL); regulatory T cells (Tregs); vaccination.

Figure 1

Proposed mechanisms of ApoB-related vaccines. (A) Before vaccination, naïve and differentiated ApoB-reactive (ApoB⁺) CD4⁺ T cells exist. In healthy individuals, these mainly comprise T_regs. (B) Shortly after vaccination, antigen-presenting cells (APCs) present ApoB-peptides in MHC-II molecules to cognate naïve CD4⁺ T cells, which become activated. Activated CD4⁺ T cells proliferate and differentiate into effector subsets (T_eff) including regulatory (T_regs) and follicular helper (T_FH) cells. The differentiation is dependent on the cytokine milieu and costimulatory signals. (C) T_regs confer atheroprotection through various mechanisms including secretion of anti-inflammatory cytokines and inhibition of ApoB⁺ T_eff cells. (D) T_FH cells aid in differentiation of B cells into plasma cells and memory B cells. Plasma cells produce high-affinity anti-ApoB IgG antibodies that confer atheroprotection via promotion of LDL clearance. Created with BioRender.com.