Immunization against angiotensins for the treatment of hypertension

Abstract

Current vaccination approaches against hypertension target angiotensin I and angiotensin II, key components of the renin-angiotensin system. The effectiveness and long-term safety of blockade of the renin-angiotensin system with antihypertensive small-molecule drugs is well documented. Phase I/II testing of the angiotensin I vaccine PMD3117 demonstrated safety and immunogenicity in humans. While angiotensin I-specific antibodies were induced blood pressure was not lowered, presumably due to insufficient antibody levels. A second vaccine, which targets angiotensin II, has been clinically tested. Administration of CYT006-AngQb to subjects with mild to moderate hypertension was safe and well tolerated. After three administrations of 300 microg of the vaccine, ambulatory blood pressure was significantly reduced compared to placebo. The vaccine was particularly effective early in the morning as systolic and diastolic blood pressure were lowered by -25 mm Hg and -13 mm Hg, respectively. Further studies are required to show long-term safety and to assess how robust and long-lived the blood pressure reduction is. It will also be important to ascertain whether the strong reduction of blood pressure in the early morning, when most cardiovascular events occur, might result in long-term benefits over current therapies.