Original papers: Therapeutic prospectiveA vaccine for hypertension based on virus-like particles: preclinical efficacy and phase I safety and immunogenicityAmbühl, Patrice Ma,*; Tissot, Alain Cb,*; Fulurija, Almab,*; Maurer, Patrikb; Nussberger, Juergc; Sabat, Robertd; Nief, Veraa; Schellekens, Charlotteb; Sladko, Katjab; Roubicek, Kirstenb; Pfister, Thomasb; Rettenbacher, Manfredb; Volk, Hans-Dietere; Wagner, Frankf; Müller, Philippb; Jennings, Gary Tb; Bachmann, Martin Fb Author Information aRenal Division, University Hospital, Zurich, Switzerland bCytos Biotechnology AG, Zurich–Schlieren, Switzerland cDivision of Angiology and Hypertension, CHUV, Lausanne, Switzerland dInterdisciplinary group of Molecular Immunopathology, Dermatology/Medical Immunology, Berlin eInstitute of Medical Immunology, Charite, Berlin fCharité Research Organisation, Berlin, Germany *The first three authors contributed equally to this work. Received 15 May, 2006 Revised 17 August, 2006 Accepted 21 August, 2006 Correspondence and requests for reprints to Martin F. Bachmann, Cytos Biotechnology AG, Wagistrasse 25, 8952 Schlieren, Switzerland Tel: +41 44 7334747; fax: +41 44 7334740; e-mail: [email protected] Conflicts of interest: P.M.A., J.N., R.S., H-D.V. and F.W. have received research funding from Cytos Biotechnology AG. A.C.T., A.F., P.M., C.S., K.S., K.R., T.P., M.R., P.M., G.T.J. and M.F.B. are employees of Cytos Biotechnology AG and have stock options or stock holdings in Cytos. Part of this work has been presented as an abstract at the scientific sessions of the American Heart Association 2005 (no. 2445, Circulation 2005; 112:II–511). Journal of Hypertension: January 2007 - Volume 25 - Issue 1 - p 63-72 doi: 10.1097/HJH.0b013e32800ff5d6 Buy Metrics Abstract Background Despite the availability of efficacious drugs, the success of treating hypertension is limited by patients' inconsistent drug intake. Immunization against angiotensin II may offer a valuable alternative to conventional drugs for the treatment of hypertension, because vaccines induce relatively long-lasting effects and do not require daily dosing. Here we describe the preclinical development and the phase I clinical trial testing of a virus-like particle (VLP)-based antihypertensive vaccine. Methods and results An angiotensin II-derived peptide was conjugated to the VLP Qβ (AngQb). AngQb was highly immunogenic in mice and rats. To test for efficacy, spontaneously hypertensive rats (SHR) were immunized with 400 μg AngQb or VLP alone. Group mean systolic blood pressure (SBP) was reduced by up to 21 mmHg (159 ± 2 versus 180 ± 5 mmHg, P < 0.001), and total angiotensin II levels (antibody-bound and free) were increased ninefold (85 ± 20 versus 9 ± 1 pmol/l, P = 0.002) compared with VLP controls. SHR treated with the angiotensin-converting enzyme (ACE) inhibitor ramipril (1 mg/kg per day by mouth) reached an SBP of 155 ± 2 mmHg. Twelve healthy volunteers of a placebo-controlled randomized phase I trial were injected once with 100 μg AngQb. Angiotensin II-specific antibodies were raised in all subjects (100% responder rate) and AngQb was well tolerated. Conclusions AngQb reduces blood pressure in SHR to levels obtained with an ACE inhibitor, and is immunogenic and well tolerated in humans. Therefore, vaccination against angiotensin II has the potential to become a useful antihypertensive treatment providing long-lasting effects and improving patient compliance. © 2007 Lippincott Williams & Wilkins, Inc.