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A novel vaccine targeting β1-adrenergic receptor

Hypertension Research volume 46, pages 1582–1595 (2023)Cite this article

Abstract

Beta-blockers are widely used in the treatment of hypertension, heart failure and ischemic heart disease. However, unstandardized medication results in diverse clinical outcomes in patients. The main causes are unattained optimal doses, insufficient follow-up and patients’ poor adherence. To improve the medication inadequacy, our team developed a novel therapeutic vaccine targeting β1-adrenergic receptor (β1-AR). The β1-AR vaccine named ABRQβ-006 was prepared by chemical conjugation of a screened β1-AR peptide with Qβ virus like particle (VLP). The antihypertensive, anti-remodeling and cardio-protective effects of β1-AR vaccine were evaluated in different animal models. The ABRQβ-006 vaccine was immunogenic that induced high titers of antibodies against β1-AR epitope peptide. In the NG-nitro-L-arginine methyl ester (L-NAME) + Sprague Dawley (SD) hypertension model, ABRQβ-006 lowered systolic blood pressure about 10 mmHg and attenuated vascular remodeling, myocardial hypertrophy and perivascular fibrosis. In the pressure-overload transverse aortic constriction (TAC) model, ABRQβ-006 significantly improved cardiac function, decreased myocardial hypertrophy, perivascular fibrosis and vascular remodeling. In the myocardial infarction (MI) model, ABRQβ-006 effectively improved cardiac remodeling, reduced cardiac fibrosis and inflammatory infiltration, which was superior to metoprolol. Moreover, no significant immune-mediated damage was observed in immunized animals. The ABRQβ-006 vaccine targeting β1-AR showed the effects on hypertension and heart rate control, myocardial remodeling inhibition and cardiac function protection. These effects could be differentiated in different types of diseases with diverse pathogenesis. ABRQβ-006 could be a novel and promising method for the treatment of hypertension and heart failure with different etiologies.

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Acknowledgements

This work was supported by the General Project of the National Natural Science Foundation of China (Nos. 81974055, 82070522, 81974106, 82070378).

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Author notes

  1. These authors contributed equally: Fan Ke, Wenlong Kuang, Xiajun Hu.

Authors and Affiliations

  1. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Fan Ke, Wenlong Kuang, Xiajun Hu, Chang Li, Wenrui Ma, Dingyang Shi, Xin Li, Zhijie Wu, Yanzhao Zhou, Yuhua Liao, Zhihua Qiu & Zihua Zhou

  2. Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Fan Ke, Wenlong Kuang, Xiajun Hu, Chang Li, Wenrui Ma, Dingyang Shi, Xin Li, Zhijie Wu, Yanzhao Zhou, Yuhua Liao, Zhihua Qiu & Zihua Zhou

  3. Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Fan Ke, Wenlong Kuang, Xiajun Hu, Chang Li, Wenrui Ma, Dingyang Shi, Xin Li, Zhijie Wu, Yanzhao Zhou, Yuhua Liao, Zhihua Qiu & Zihua Zhou

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Contributions

FK, WK, XH, ZQ and ZZ conceptualized the project. FK, WK and XH performed experiments. CL, WM, DS and ZW analyzed and interpreted data. XL analyzed the statistics. YZ and YL provided technical guidance. FK, WK and XH wrote the manuscript. YL, ZQ and ZZ supplied funds support. Co-first authors are ranked in the order in which they participated in the experiment. All authors reviewed the manuscript and discussed the work.

Corresponding authors

Correspondence to Zhihua Qiu or Zihua Zhou.

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Conflict of interest

The authors declare no competing interests.

Ethics statement

This study was strictly performed according to the recommendations in the Guide for the Care and Use of Laboratory Animals (Science & Technology Department of Hubei Province, China, 2005). The protocol was approved by Animal Care and Use Committee of Hubei Province (Nos. 110324211101061211, 42010200003531, 110011211112453856 and 42010200007174). The animals were fed in a specific pathogen-free animal housing facility with 22  °C  ±  2  °C temperature, 60% ±5% relative humidity and a 12:12 light: dark cycle. Sterile water and rodent chow were available ad libitum. Every effort was made to minimize animal pain, suffering and distress and to reduce the numbers of animals used. All surgeries were performed under sodium pentobarbital anesthesia.

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Ke, F., Kuang, W., Hu, X. et al. A novel vaccine targeting β1-adrenergic receptor. Hypertens Res 46, 1582–1595 (2023). https://doi.org/10.1038/s41440-023-01265-3

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