Elsevier

Atherosclerosis

Volume 335, October 2021, Pages 89-97
Atherosclerosis

Promoting athero-protective immunity by vaccination with low density lipoprotein-derived antigens

https://doi.org/10.1016/j.atherosclerosis.2021.08.033Get rights and content
Under a Creative Commons license
open access

Highlight

  • LDL particles oxidized in the arterial intima become targeted by the immune system.

  • Both athero-protective and pro-atherogenic immune responses exist.

  • Immunomodulatory therapies that promote atheroprotective immune responses represents a possible future therapy.

  • Vaccines stimulating tolerance for neoantigens formed in oxidized LDL represents one example of such therapies.

Abstract

Immune responses activated by LDL particles that have been trapped and oxidized in the arterial wall play an important role in atherosclerosis. Some of these immune responses are protective by facilitating the removal of pro-inflammatory and toxic lipid species formed as result of LDL oxidation. However, should these protective immune responses be insufficient, other more potent pro-inflammatory immune responses instead contributing to disease progression will gradually become dominant. The importance of the balance between protective and pathogenic immunity is particularly apparent when it comes to the adaptive immune system where pro-inflammatory T helper 1 (Th1) type T cells aggravate atherosclerosis, while regulatory T cells (Tregs) have an opposing role. As oxidized LDL is a key autoantigen in atherosclerosis, it has become an interesting possibility that immune-modulatory therapy that favors the activity of apolipoprotein B peptide-specific Tregs could be developed into a novel treatment strategy for prevention/stabilization of atherosclerosis and ischemic cardiovascular events. Indeed, several such oxidized LDL tolerance vaccines have shown promising results in animal models of atherosclerosis. This review will discuss the experimental background for development of atherosclerosis vaccines based on LDL-derived antigens as well as the challenges involved in translating these findings into clinical application.

Keywords

Atherosclerosis
T cells
Antibodies
Vaccination
Low density lipoprotein

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