title: Therapeutic vaccines against human and rat renin in spontaneously hypertensive rats.
abstract: Vaccination provides a promising approach for treatment of hypertension and improvement in compliance. As the initiation factor of renin-angiotensin system, renin plays a critical role in hypertension. In this study, we selected six peptides (rR32, rR72, rR215, hR32, hR72, and hR215) belonging to potential epitopes of rat and human renin. The main criteria were as follows: (1) include one of renin catalytic sites or the flap sequence; (2) low/no-similarity when matched with the host proteome; (3) ideal antigenicity and hydrophilicity. The peptides were coupled to keyhole limpet hemocyanin and injected into SpragueDawley (SD) rats, spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats. The antisera titers and the binding capacity with renin were detected. The effects of the anti-peptides antibodies on plasma renin activity (PRA) and blood pressure were also determined. All peptides elicited strong antibody responses. The antisera titers ranged from 1:32,000 to 1:80,000 in SD rats on day 63. All antisera could bind to renin in vitro. Compared with the control antibody, the antibodies against the rR32, hR32, rR72 and hR72 peptides inhibited PRA level by up to about 50%. Complete cross-reactivity of the anti-rR32 antibody and the anti-hR32 antibody was confirmed. The epitopes rR32 and hR32 vaccines significantly decreased systolic blood pressure (SBP) of SHRs up to 15mmHg (175±2 vesus 190±3 mmHg, P = 0.035; 180±2 vesus 195±3 mmHg, P = 0.039), while no obvious effect on SD rats. Additionally, no significant immune-mediated damage was detected in the vaccinated animals. In conclusion, the antigenic peptide hR32 vaccine mimicking the (32)Asp catalytic site of human renin may constitute a novel tool for the development of a renin vaccine.
authors.affiliation: Laboratory of Cardiovascular Immunology, Key Laboratory of Molecular Targeted Therapies of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Qiu
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Yanzhao
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jibin
authors.initials: J
authors.lastname: Lin
authors.forename: Dan
authors.initials: D
authors.lastname: Ding
authors.forename: Shijun
authors.initials: S
authors.lastname: Yang
authors.forename: Fen
authors.initials: F
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Xian
authors.initials: X
authors.lastname: Yu
authors.forename: Zihua
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Liao
mesh_terms: D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000918:Antibody Specificity; D000959:Antihypertensive Agents / Q000737:chemistry / Q000276:immunology*; D001794:Blood Pressure / Q000276:immunology; D020134:Catalytic Domain; D003429:Cross Reactions; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology*
chemical_list: D000959:Antihypertensive Agents; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D000804:Angiotensin II; D012083:Renin