Randomized double-blind placebo-controlled study of an angiotensin immunotherapeutic vaccine (PMD3117) in hypertensive subjects

Abstract

Immunization against components of the renin-angiotensin system offers a potential alternative to daily medication in some patients with hypertension or heart failure. Our primary objective was to determine whether a sustained antibody titre to Ang I (angiotensin I) can be achieved in hypertensive patients. The secondary objective was to determine whether the antibodies block the renin system. Patients (n=27) with essential hypertension responsive to an ACEi (angiotensin-converting enzyme inhibitor) or ARB (angiotensin blocker) were randomly assigned to receive three or four injections of the Ang I vaccine PMD3117 or aluminium hydroxide (Alhydrogel trade mark ) over a 6 week period. Antibody titre was measured prior to each injection and every 30 days until disappearance. Indices of renin blockade were changes in renin and aldosterone (blood and urine) and a within-patient comparison of the pre- and post-vaccination rise in 24 h ambulatory blood pressure after 2 weeks of withdrawal of ACEi or ARB. The anti-(Ang I) antibody titre rose from the second injection in both regimes and peaked on day 64. Median half-life was 85 (95% CI, 44 and 153) days (where CI is confidence interval). Vaccination did not influence blood pressure, but significantly blunted the fall in plasma renin following withdrawal of ACEi or ARB. At 42 days after the first injection, aldosterone excretion was decreased by PMD3117 to 6 (95% CI, 1 and 31)% of values in patients receiving Alhydrogel trade mark (P=0.012). In patients with essential hypertension, PMD3117 generated a prolonged antibody response to Ang I. Biochemical measurements show evidence of blockade of the renin system, but higher titres will be required to achieve a decrease in blood pressure.

Effectiveness and Safety of a Therapeutic Vaccine Against Angiotensin II Receptor Type 1 in Hypertensive Animals

“…27 However, neither BP nor aldosterone concentration in blood secretion was significantly modifed by angiotensin I immunization in humans. 28 The Ang II vaccine CYT-006-AngQb is a promising therapeutic vaccine based on VLP carrier. Clinical data demonstrated that vaccination with CYT-006-AngQb led to a significant reduction in SBP and no serious adverse events in hypertensive patients.…”

New Approaches in the Treatment of Hypertension

“…114 An Ang I vaccine also lowered BP in animal models, 115,116 but was ineffective in a randomized, doubleblind, placebo-controlled clinical trial. 117 Further, a vaccine raised in response to an Ang II-derived peptide conjugated to a virus-like particle derived from the bacteriophage Qβ (AngQb) was effective in producing anti-Ang II antibodies and reducing BP in SHR, despite increasing circulating Ang II levels 118 (Figure 2; Table). In a placebo-controlled, randomized phase I trial, 12 healthy volunteers received a single injection of AngQb.…”

Vaccination against the angiotensin type 1 receptor for the prevention of L-NAME-induced nephropathy

“…10 A vaccine against Ang I was tested in a phase IIa clinical trial, and was found to be safe, but did not effectively cause a decrease in BP in patients with essential hypertension. 11 In contrast, the study by Tissot et al 8 using a vaccine against Ang II showed a small, but significant, decrease in both systolic and diastolic BP in patients with mild-to-moderate hypertension. Furthermore, Zhu et al 12 reported that a vaccine against the Ang II type 1 (AT1) receptor was effective in reducing BP in rats.…”