Whether and Why Do We Need a Vaccine Against Atherosclerosis? Can We Expect It Anytime Soon?

Abstract

Purpose of Review Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of premature death. Lipid disorders, particularly elevated serum low-density lipoprotein cholesterol (LDL-C), contribute significantly to ASCVD. The risk of developing ASCVD is influenced by the duration of exposure to elevated LDL-C concentrations (cholesterol-years concept). Implementing lipid-lowering treatments based on the principles of “the earlier the better,” “the lower the better,” and “the longer the better” has been shown to reduce cardiovascular risk and significantly extend lifespan. Despite the availability of numerous lipid-lowering drugs, achieving satisfactory control of lipid disorders remains very challenging. Therefore, there is a need for novel approaches to improve treatment adherence. Recent Findings One promising solution under investigation is the development of an anti-PCSK9 vaccine, which could be administered annually to provide long-term control over LDL-C concentrations. Experimental studies and the sole clinical trial conducted thus far have demonstrated that the anti-PCSK9 vaccine induces a durable immune response associated with lipid-lowering and anti-atherosclerotic effects. Furthermore, it has exhibited good tolerability and a satisfactory safety profile. However, we still need data from phase 2, 3, and cardiovascular outcome trial to confirm its safety and efficacy and add value in the armamentarium of available and perspective lipid-lowering drugs. Summary This article highlights the significance of developing an anti-PCSK9 vaccine and provides an overview of the current knowledge on various anti-PCSK9 vaccines.

Macrophage polarisation and inflammatory mechanisms in atherosclerosis: Implications for prevention and treatment

“…Recently, a new dual-stranded siRNA, called inclisiran, was developed to block PCSK9 via the degradation of PCSK9 mRNA, leading to the lowering of LDL-C concentrations in the plasma [ 78 ]. Other novel developments include three main types of PCSK9 vaccines: Peptide Vaccine AT04A (which not only reduces LDL-C but also decreases pro-inflammatory factors), Nanoliposome Anti -PCSK9 Vaccine L-IFPTA+ (which induces higher and more persistent anti -PCSK9 antibody titres compared to peptide vaccines), and Virus-Like Particle (VLP) Peptide Vaccines Anti -PCSK9 Qβ-003 (which reduces lipid levels and also exhibits anti-fibrotic effects related to regulating fatty acid β-oxidation) [ 78 , 79 ].…”

Development of a PCSK9-targeted nanoparticle vaccine to effectively decrease the hypercholesterolemia

“… 26 Recently, experimental immunization strategies targeting PCSK9 as potential treatment for hypercholesterolemia have been developed. 27 , 28 , 29 , 30 , 31 Designing and constructing the PCSK9 vaccine is of great scientific significance, as it aims to improve the immunogenicity of this autoantigen. In recent years, nanoparticle (NP) vaccines have been used in the development of vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).…”