Division of Inflammation Biology, La Jolla Institute for Immunology, 9420, Athena Circle Drive, La Jolla, CA 92037, USA.
Division of Inflammation Biology, La Jolla Institute for Immunology, 9420, Athena Circle Drive, La Jolla, CA 92037, USA; Division of Vaccine Science, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Vaccine. 2020 Jun 9;38(28):4495-4506. doi: 10.1016/j.vaccine.2019.12.039. Epub 2020 Jan 19.
Atherosclerosis, the major underlying cause of cardiovascular diseases (CVD), is the number one killer globally. The disease pathogenesis involves a complex interplay between metabolic and immune components. Although lipid-lowering drugs such as statins curb the risks associated with CVD, significant residual inflammatory risk remains. Substantial evidence from experimental models and clinical studies has established the role of inflammation and immune effector mechanisms in the pathogenesis of atherosclerosis. Several stages of the disease are affected by host-mediated antigen-specific adaptive immune responses that play either protective or proatherogenic roles. Therefore, strategies to boost an anti-atherogenic humoral and T regulatory cell response are emerging as preventative or therapeutic strategies to lowering inflammatory residual risks. Vaccination holds promise as an efficient, durable and relatively inexpensive approach to induce protective adaptive immunity in atherosclerotic patients. In this review, we discuss the status and opportunities for a human atherosclerosis vaccine. We describe (1) some of the immunomodulatory therapeutic interventions tested in atherosclerosis (2) the immune targets identified in pre-clinical and clinical investigations (3) immunization strategies evaluated in animal models (4) past and ongoing clinical trials to examine the safety and efficacy of human atherosclerosis vaccines and (5) strategies to improve and optimize vaccination in humans (antigen selection, formulation, dose and delivery).
动脉粥样硬化是心血管疾病（CVD）的主要潜在原因，是全球头号杀手。该疾病的发病机制涉及代谢和免疫成分之间的复杂相互作用。尽管降脂药物如他汀类药物可以降低与 CVD 相关的风险，但仍然存在显著的炎症残留风险。实验模型和临床研究的大量证据已经确立了炎症和免疫效应机制在动脉粥样硬化发病机制中的作用。宿主介导的抗原特异性适应性免疫反应在疾病的几个阶段都受到影响，这些反应发挥保护或促动脉粥样硬化作用。因此，增强抗动脉粥样硬化的体液和 T 调节细胞反应的策略正在成为降低炎症残留风险的预防或治疗策略。疫苗接种作为一种有效的、持久的和相对廉价的方法，有望在动脉粥样硬化患者中诱导保护性适应性免疫。在这篇综述中，我们讨论了人类动脉粥样硬化疫苗的现状和机遇。我们描述了（1）在动脉粥样硬化中测试的一些免疫调节治疗干预措施，（2）在临床前和临床研究中确定的免疫靶标，（3）在动物模型中评估的免疫接种策略，（4）过去和正在进行的临床试验，以检查人类动脉粥样硬化疫苗的安全性和有效性，以及（5）改善和优化人类疫苗接种的策略（抗原选择、配方、剂量和传递）。
