Table 1. Summary of important preclinical and clinical trials of vaccines against hypertension.

Author (Year)	Type of vaccine	Phase of trial	Sample size	Location	Outcome
Graham et al. (1970)30	Ang II with Bovine serum albumin/ Freund's adjuvant	Preclinical	12 rabbits	United Kingdom	No decrease in blood pressure resulted in termination of trial.
Michel JB et al. (1987, 1990)31,32	Pure human renin with Freund's adjuvant	Preclinical	10 SHRs, 10 normotensive rats, and 8 male marmosets	France	High titer of renin antibodies and significant decrease in systolic blood pressure but development of an autoimmune disease localized in the kidney caused termination of the trial.
Reade R et al. (1989)33	Ang1 vaccine coupled with Limulus polyphemus hemocyanin	Preclinical	50 SHRs	France	Raised antibody titer, but did not reduce blood pressure.
Gardiner SM et al. (2000)34	AngI analog conjugated with a tetanus toxoid carrier protein and adjuvanted with aluminum hydroxide (PMD-2850)	Preclinical	82 male, Sprague-Dawley rats	England	Pressor responses to AngI were significantly inhibited but responses to AngII were unaffected.
Downham MR et al. (2003)35	AngI analog vaccine conjugated with keyhole limpet hemocyanin (PMD3117) and PMD-2850 vaccine	Phase 1 clinical trial	12 male, Sprague-Dawley rats and 50 healthy, male, human volunteers	United Kingdom	Both showed anti-AngI responses but did not cause reduction in blood pressure.
Brown M et al. (2004)36	PMD3117 vaccine	Phase 2 clinical trial Randomized double-blind placebo-controlled	27 patients with essential hypertension	United Kingdom	Only PMD3117 vaccine evidenced blockade of the renin system and rise in antibody titer but not influenced blood pressure
Zhu et al. (2006)39	AngII-type 1A receptor (ATR12181) with TT/ Freund's adjuvant	Preclinical	12 SHRs	China	Repeated immunization lowers blood pressure, decreases cardiac hypertrophy. No auto-immune disease detected
Tissot et al. (2008)42	AngII (AngQb) with VLP/ALOH	Phase 2 clinical trial	72 patients with mild to moderate hypertension	Switzerland	Significant blood pressure decrease in mean blood pressure. Safe, tolerable, and long half-life (4 mo).
Turkie WH et al. (2010)37	Angiotensin therapeutic vaccine (ATV) by using novel adjuvant, CoVaccine HT™	Phase 2b clinical trial Randomized, double blind, placebo controlled	124 patients with mild to moderate hypertension	United Kingdom	Terminated due to dose limiting adverse effects.
Hong F et al. (2011)43	Antiangiotensin peptide AngI-R	Preclinical	27 SHRs	China	Decrease the blood pressure of SHRs, increase in anti-AngI/II antibody titer.
Chen et al. (2013)44	Human angiotensin II (Ang II) receptor type 1 conjugated with Qβ bacteriophage virus-like particles	Preclinical	40 mice, 36 SHRs	China	Decreased the blood pressure of Ang II–induced hypertensive mice and spontaneously hypertensive rats effectively.
Ou X et al. (2013)40	chimeric protein named pHAV–4Ang IIs	Preclinical	20 SHRs	China	Decrease blood pressure in SHRs

^*SHRs, spontaneous hypertensive rats; VLP, virus like particle; ALOH, aluminum hydroxide; pHAV, protein hepatitis A virus.