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 32Asp catalytic site of human renin may constitute a novel tool for the development of a renin vaccine.
Highlights
Hypertension has become a leading disease in both developed and undeveloped countries [1]
To evaluate reninangiotensin system (RAS) activity of SD rats, the plasma renin activity (PRA) and angiotensin II (Ang II) concentration were determined on day 63
Compared with the control group, the PRA was significantly decreased in the rR32, hR32, and rR72 groups (Figure 1B), while Ang II concentration only tend to be decreased in these groups (Figure 1C)
Summary
Hypertension has become a leading disease in both developed and undeveloped countries [1]. To address the compliance issue and improve therapeutic outcomes for patients, it is necessary to develop novel methods for hypertension treatment. Renin vaccine interferes with the initial and rate-limiting step of RAS cascade [3]. The development of renin vaccine is seemed an attractive choice [4,5]. Renin was first used to immunize the animals as a vaccine against RAS [6]. The renin vaccine could lower the BP of animals, but was accompanied by severe autoimmune kidney diseases [7,8]. Vaccination with renin may be an effective method to block RAS and decrease BP, while the safety concerns impeded its progress. No successful renin vaccines have been developed
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