Success and failure of vaccines against renin-angiotensin system components.

Therapeutic vaccination pre-dated modern drugs as a possible strategy for treating hypertension. This approach is now being rediscovered, through use of modified angiotensins as immunogens together with carriers and adjuvants. Effective blockade of the renin-angiotensin system (RAS) with treatment twice a year might suit patients who dislike taking drugs on a daily basis and would also be an attractive option for those who have blood pressures in the prehypertensive range, if it can prevent hypertension itself from developing. Proof of concept with a vaccine whose efficacy is easy to measure will encourage development of further vaccines directed against targets such as aldosterone or other pathways where alternative treatments are scarce or absent. Two angiotensin-based vaccines are currently in development: PMD3117 comprises modified angiotensin I coupled to keyhole limpet hemocyanin, and Cyt006-AngQb is a conjugate of angiotensin II linked to virus particles. Early phase II studies in patients with hypertension demonstrated some efficacy, but the vaccines are not as effective as existing inhibitors of the RAS. Large studies now in progress will establish whether further modification of the immunogen or adjuvant is required to boost antibody titers.