CC BY-NC-ND 4.0 · Hamostaseologie 2021; 41(06): 447-457
DOI: 10.1055/a-1661-1908
Review Article

Modulating Autoimmunity against LDL: Development of a Vaccine against Atherosclerosis

Timoteo Marchini
1  Cardiology and Angiology I, University Heart Center and Medical Center – University of Freiburg, Germany
2  Faculty of Medicine, University of Freiburg, Freiburg, Germany
3  Facultad de Farmacia y Bioquímica, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina
4  Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Germany
,
Tijani Abogunloko
1  Cardiology and Angiology I, University Heart Center and Medical Center – University of Freiburg, Germany
2  Faculty of Medicine, University of Freiburg, Freiburg, Germany
4  Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Germany
,
Dennis Wolf
1  Cardiology and Angiology I, University Heart Center and Medical Center – University of Freiburg, Germany
2  Faculty of Medicine, University of Freiburg, Freiburg, Germany
› Author Affiliations
Funding This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 853425). T.M. and D.W. are members of the SFB1425, funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).

Abstract

Atherosclerosis is a chronic inflammatory disease of the arterial wall that leads to the build-up of occluding atherosclerotic plaques. Its clinical sequelae, myocardial infarction and stroke, represent the most frequent causes of death worldwide. Atherosclerosis is a multifactorial pathology that involves traditional risk factors and chronic low-grade inflammation in the atherosclerotic plaque and systemically. This process is accompanied by a strong autoimmune response that involves autoreactive T cells in lymph nodes and atherosclerotic plaques, as well as autoantibodies that recognize low-density lipoprotein (LDL) and its main protein component apolipoprotein B (ApoB). In the past 60 years, numerous preclinical observations have suggested that immunomodulatory vaccination with LDL, ApoB, or its peptides has the potential to specifically dampen autoimmunity, enhance tolerance to atherosclerosis-specific antigens, and protect from experimental atherosclerosis in mouse models. Here, we summarize and discuss mechanisms, challenges, and therapeutic opportunities of immunomodulatory vaccination and other strategies to enhance protective immunity in atherosclerosis.

Zusammenfassung

Die Atherosklerose stellt eine chronisch entzündliche Erkrankung der Arterienwand dar, die zur Bildung von Gefäß-verengenden atherosklerotischen Plaques führt. Ihre klinischen Folgen, Herzinfarkt und Schlaganfall, repräsentieren die weltweit häufigsten Todesursachen. Der Erkrankung liegt ein multifaktorieller Krankheitsprozess zu Grunde, der traditionelle Risikofaktoren und eine chronische lokale und systemische Entzündungsreaktion umfasst. Die Entstehung der Atherosklerose wird von einer starken Autoimmunreaktion begleitet, an der autoreaktive T-Zellen in Lymphknoten und atherosklerotischen Plaques sowie Autoantikörper beteiligt sind, die gegen low-density lipoprotein (LDL) Cholesterin und Apolipoprotein B (ApoB) gerichtet sind. Vielfältige präklinische Untersuchungen aus den vergangenen 60 Jahren konnten zeigen, dass eine immunmodulatorische Impfung mit LDL, ApoB und ApoB-Peptiden das Potenzial hat, die Autoimmunität in er atherosklerotischen Plaque abzuschwächen, eine Toleranz gegenüber Arteriosklerose-spezifischen Antigenen auszubauen und vor Atherosklerose in Mausmodellen zu schützen. In diesem Artikel diskutieren wir die Mechanismen, Herausforderungen und therapeutischen Möglichkeiten einer immunmodulatorischen Impfung und anderer Strategien, die zur einer Stärkung der protektiven Immunantwort in der Atherosklerose führen.



Publication History

Received: 05 July 2021

Accepted: 04 October 2021

Publication Date:
23 December 2021 (online)

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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