高血压患者有望不用每天吃药，每1到3个月打一针疫苗，就能平稳血压。近日，武汉协和医院心内科教授廖玉华耗时8年，带领团队在“高血压疫苗”研究上取得重大进展。上月26日，相关论文在国际高血压领域最权威期刊《Hypertension》上发表，该研究成果已获得国家发明专利，成为国内自主研发的首个高血压疫苗。
8年研制出降压疫苗
廖玉华教授团队自主研发的是ATRQβ-001疫苗。据介绍，和正常人注射用来预防疾病的疫苗不同，这是为高血压患者研制的、可替代药物进行治疗的针剂。
在廖玉华多年的临床治疗中，率先发现一些高血压患者体内存在一种自身抗体，这些抗体会引起高血压和心血管损害。这一发现，“刺激”了团队的研究思路如果反其道而行之，能不能把这些抗体当做“靶心”，对它们进行针对性治疗，产生一种具有阻止作用的抗体，并将其制成疫苗，用于治疗高血压。
随后，研究小组进行了长达8年的研究，通过对老鼠分批次、反复试验，最终筛选出ATRQβ-001疫苗。廖教授说，试验选择的是“自发性高血压大鼠”，也就是说，老鼠生长到12周，血压会自然升高，适合做高血压病动物研究。
结果发现，疫苗可有效抑制老鼠体内某些可引起血压升高的物质，让老鼠的血压明显下降，对老鼠的心、肾、血管等有明显的保护作用。
目前，这项研究成果已获得国家发明专利，成为国内自主研发的首个高血压疫苗。上月26日，论文在国际高血压领域最权威期刊《Hypertension》上发表。
患者每1至3个月注射一针
据流行病学调查显示，中国有超过2亿的成人高血压患者，但疾病的控制率仅为6.1%。廖玉华介绍，传统口服药物的治疗方法比较成熟，但患者依从性太差，因为经济、生活方式等多方面原因，很难坚持每天吃药，有的不按时吃，有的一见好转擅自停药，都可能出现大问题。
“相比之下，疫苗的有效时间要长得多，患者每1至3个月注射一次，保证体内抗体水平。”廖教授说，如过人体试验后，证实疫苗对人体有效且安全，患者不用每天捧着药丸了。
廖教授坦言，研究从实验室走向临床，还得经过漫长过程，需要制药企业积极参与开发研究，经过毒理、药理、安全性评价后，并在大型灵长类动物或哺乳动物中做试验，确认无副作用；得到国家药监部门批文，才能用于临床试验一、二、三、四期等阶段，样本达上万人。预计一切顺利，也得8到10年。
Effectiveness and Safety of a Therapeutic Vaccine Against Angiotensin II Receptor Type 1 in Hypertensive Animals
Xiao Chen, Zhihua Qiu, Shijun Yang, Dan Ding, Fen Chen, Yanzhao Zhou, Min Wang, Jibin Lin, Xian Yu, Zihua Zhou, Yuhua Liao
Primary hypertension is a chronic disease with high morbidity, and the rate of controlled blood pressure is far from satisfactory, worldwide. Vaccination provides a promising approach for treatment of hypertension and improvement in compliance. Here, the ATRQβ-001 vaccine, a peptide (ATR-001) derived from human angiotensin II (Ang II) receptor type 1 conjugated with Qβ bacteriophage virus-like particles, was developed and evaluated in animal models of hypertension. The ATRQβ-001 vaccine significantly decreased the blood pressure of Ang II–induced hypertensive mice up to 35 mm Hg (143±4 versus 178±6 mm Hg; P=0.005) and that of spontaneously hypertensive rats up to 19 mm Hg (173±2 versus 192±3 mm Hg; P=0.003) and prevented remodeling of vulnerable hypertensive target organs. No obvious feedback activation of circulating or local renin-angiotensin system was observed. Additionally, no significant immune-mediated damage was detected in vaccinated hypertensive and nonhypertensive animals. The half-life of the anti-ATR-001 antibody was 14.4 days, surpassing that of existing chemical drugs. In vitro, the anti–ATR-001 antibody specifically bound to Ang II receptor type 1 and inhibited Ca2+-dependent signal transduction events, including protein kinase C-α translocation, extracellular signal-regulated kinase 1/2 phosphorylation (72% decrease; P=0.013), and elevation of intracellular Ca2+ (68% decrease; P=0.017) induced by Ang II, but without inhibiting Ang II binding to the receptor. In conclusion, the ATRQβ-001 vaccine decreased the blood pressure of Ang II–induced hypertensive mice and spontaneously hypertensive rats effectively through diminishing the pressure response and inhibiting signal transduction initiated by Ang II. Thus, the ATRQβ-001 vaccine may provide a novel and promising method for the treatment of primary hypertension.
