**12. Vaccines**

The first attempts to produce a vaccine for hypertension was conducted in the early 50s of the twentieth century and were focused on the RAAS. At that time immunogen renin was employed, demonstrating an antihypertensive action. However, its development was abandoned when observing the appearance of an autoimmune disease characterized by the deposition of antibodies antirenin in the juxtaglomerular apparatus and progressive interstitial inflammatory lesion in the kidney in animal models studied. (Goldblatt, Haas & Lamfrom, 1951, Michel et al., 1987)

Years later in the 60s, interest is focused on vaccines used against Ang I, but these had no antihypertensive effect. (Downham et al., 2003) At present, interest is focused on Ang II as an immunogen agent using a new immunization technology that combines antigens on the surface of a structure of virus like particles (VLP) generating a B cell response against autoantigens. VLPs conjugated to Ang II (CYT006-AngQb vaccine) have been tested in preclinical and clinical trials and have been observed to be well tolerated, immunogenic and with a high proportion of respondent individuals.

In Phase I studies, the tolerability, safety and immunogenicity of the vaccine was assessed after injection of the vaccine in 12 healthy subjects. They noted that the vaccine was well tolerated, safe and rapidly produced levels of specific antibodies to Ang II, which descended over time. (Ambühl et al., 2007) In Phase II B trials, in order to evaluate the effective response dose, the effect of the administration of 100 or 300 micrograms of the vaccine (CYT006-AngQb) or placebo to 72 patients (65 men and seven women with a average age 51.5 years) with moderate hypertension had been analyzed. The administration of the vaccine or placebo was performed at zero, four and twelve weeks. After twelve weeks of follow up, we observed that vaccination with CYT006-AngQb induced a dose dependent response, so that the title of antibodies to Ang II was greater in patients who received doses of 300 micrograms. The BP changes were evaluated at week 14. It was observed that patients who received 300 micrograms of vaccine significantly reduced the daytime systolic BP by 5.6 mmHg and diastolic by 2.8 mmHg compared with placebo recipients. (Tissot et al., 2008)

However, more studies on the beneficial effects of vaccination against hypertension are still needed, its long term effects, its influence on target organ damage and mortality.
