Abstract 2519: CYT006-AngQb, a Vaccine Against Hypertension Targeting Angiotensin II, Reduces Early-Morning and Day-Time Blood Pressure
Immunisation against angiotensin II may offer a valuable alternative to conventional drugs for the treatment of hypertension by tackling the main limitation to successful therapy: the patients’ inconsistent drug intake. CYT006-AngQb, a virus-like-particle based conjugate vaccine targeting angiotensin II (Ang II), was shown to induce antibodies against Ang II and to reduce day-time ambulatory systolic blood pressure (SBP) in a multicenter, double blind, randomized, placebo-controlled phase IIa trial in 72 mild-to-moderate hypertensive patients. The vaccine was safe and well tolerated. Three injections of either 100 or 300 μg of AngQb, or placebo (Pbo), formulated in the adjuvant aluminum hydroxide, were administered on weeks 0, 4 and 12. Ambulatory blood pressure was determined at baseline and at week 14. Plasma active renin was measured at weeks 0, 6 and 14. A strong antibody response against Ang II was raised in all vaccinated patients. This was evident even after the first injection, and could be boosted. The antibody response was significantly higher in the 300 μg than the 100 μg group (P=0.01), and was relatively long-lived with a half-life of about 4 months. In the 300 μg group, ambulatory day-time SBP and diastolic blood pressure (DBP) were reduced at week 14 compared to baseline by 5.6 (P=0.007) and 2.8 mm Hg (P=0.034), respectively. The reduction in SBP was also significant in comparison to Pbo, with a baseline-corrected difference of -5.4 mm Hg (P=0.0498). Moreover, for the 300 μg group, the morning surge in blood pressure was blunted between 5 and 8 AM (P=0.0032 / 0.022, SBP / DBP), with a baseline-corrected difference from Pbo at 8 AM of -26 / -11 mm Hg (SBP / DBP, P=0.0002 / 0.009). Plasma active renin was only slightly increased from baseline on week 14 in the 300 μg group (from 5.1 to 6.3 pg/ml, P=0.02). CYT006-AngQb reduced blood pressure in situations where the renin-angiotensin-aldosterone system is stimulated, and was particularly effective in the morning hours when most cardiovascular events occur. These effects were dependent upon the dose of vaccine and antibody levels. Furthermore, the antibody response was long-lived and reversible. These findings support further testing of the vaccine with an optimized dose regimen.