Evaluation of two carrier protein–angiotensin I conjugate vaccines to assess their future potential to control high blood pressure (hypertension) in man

• Published in: British journal of clinical pharmacology 2003-11, Vol.56 (5), p.505-512
• Main Authors: Downham, M. R., Auton, T. R., Rosul, A., Sharp, H. L., Sjöström, L., Rushton, A., Richards, J. P., Mant, T. G. K., Gardiner, S. M., Bennett, T., Glover, J. F.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; angiotensin conjugate vaccines; Angiotensin I - immunology; Animals; Antihypertensive agents; Biological and medical sciences; Cardiovascular system; Carrier Proteins - therapeutic use; Dose-Response Relationship, Immunologic; Drug Evaluation; Enzyme-Linked Immunosorbent Assay; epitopic suppression; Hemocyanins - therapeutic use; Humans; hypertension; Hypertension - immunology; Hypertension - therapy; Immunization; Immunoglobulins - immunology; Immunotherapy - methods; Male; Medical sciences; Middle Aged; Pharmacodynamics; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Tetanus Toxoid - therapeutic use; Vaccines, Conjugate - therapeutic use
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.1365-2125.2003.01926.x

Aims  We aim to modulate the renin–angiotensin system (RAS) by active immunization against angiotensin I hormone (AI), potentially providing a novel conjugate vaccine treatment for hypertension in man. Methods  Immunization studies in rat and human subjects compare the effectiveness of tetanus toxoid (TT) and keyhole limpet haemocyanin (KLH) vaccines for immunotherapy following conjugation with an AI peptide analogue (AI). Cardiovascular responses were assessed in immunized rats and human subjects (two‐dose trial only), following increasing i.v. infusions of either AI or angiotensin II hormone (AII). Results  The AI–TT and AI–KLH conjugate vaccines induced an equivalent immune response, and inhibition of the pressor effects to exogenous AI in rats. Single‐dose clinical trials with both conjugate vaccines only resulted in an immune response to the KLH carrier protein. A two‐dose clinical trial of AI–KLH conjugate vaccine resulted in a significant immune response to AI. A shift in diastolic blood pressure (DBP) dose–response was demonstrated following challenge with AI and AII for the study volunteer showing the largest anti‐AI IgG induction. Conclusion  KLH was shown to be a suitable alternative to TT as a carrier protein for AI, thus supporting continued evaluation of our AI–KLH conjugate vaccine for treatment of hypertension in man.