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治疗性疫苗治疗慢性病的未来方向。

Future Directions of Therapeutic Vaccines for Chronic Diseases.

机构信息

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine.

Department of Health Development and Medicine, Osaka University Graduate School of Medicine.

出版信息

Circ J. 2020 Oct 23;84(11):1895-1902. doi: 10.1253/circj.CJ-20-0703. Epub 2020 Sep 8.

Abstract

Vaccines are well-known therapies for infectious disease and cancer; however, recently, we and others have developed vaccines for other chronic diseases, such as hypertension, diabetes and dyslipidemia. Although we have many treatment options for hypertension, including angiotensin II type 1 receptor blockers, calcium-channel blockers, and diuretics, a substantial portion of the hypertensive population has uncontrolled blood pressure due to poor medication adherence. When these vaccines are established in the future as therapeutic options for chronic diseases, their administration regimen, such as several times per year, will replace daily medication use. Thus, therapeutic vaccines might be a novel option to control the progression of cardiovascular diseases. Importantly, regarding the development of vaccines against self-antigens (i.e., angiotensin II), the vaccine should efficiently induce a blocking antibody response against the self-antigen without provoking cytotoxic T cells. Therefore, to address the safety and efficiency of therapeutic vaccines, we have developed an original B-cell vaccine to induce antibody production and used carrier proteins, which include exogenous T-cell epitopes through the major histocompatibility complex. In this review, we will introduce the challenges in developing therapeutic vaccines for chronic diseases and describe the therapeutic potential for cardiovascular diseases.

摘要

疫苗是治疗传染病和癌症的知名疗法;然而,最近,我们和其他人已经开发出了针对其他慢性疾病的疫苗,如高血压、糖尿病和血脂异常。尽管我们有许多治疗高血压的选择,包括血管紧张素 II 型 1 型受体阻滞剂、钙通道阻滞剂和利尿剂,但由于药物依从性差,相当一部分高血压患者的血压无法得到控制。当这些疫苗在未来成为慢性疾病的治疗选择时,它们的给药方案,例如每年几次,将取代每日用药。因此,治疗性疫苗可能是控制心血管疾病进展的一种新选择。重要的是,关于针对自身抗原(即血管紧张素 II)的疫苗开发,疫苗应该有效地诱导针对自身抗原的阻断抗体反应,而不会引发细胞毒性 T 细胞。因此,为了解决治疗性疫苗的安全性和效率问题,我们开发了一种原始的 B 细胞疫苗来诱导抗体产生,并使用了载体蛋白,这些载体蛋白通过主要组织相容性复合物包含了外源性 T 细胞表位。在这篇综述中,我们将介绍开发治疗慢性疾病的治疗性疫苗所面临的挑战,并描述其在心血管疾病方面的治疗潜力。

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