ISH NIA OS-02 ATTENUATION OF HYPERTENSION BY LESS-INVASIVE INTRANASAL VACCINATION AGAINST ANGIOTENSIN II TYPE 1 RECEPTOR IN SPONTANEOUSLY HYPERTENSIVE RATS

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Abstract

Objective:

Previous studies have shown that injectable vaccines against renin-angiotensin system may be effective for the treatment of hypertension, but these injectable vaccines often cause local skin reactions and soreness at the injection site. The aim of this study was to develop a new non-injectable vaccine against angiotensin II type 1 receptor (AT1R) and examine its effect on blood pressure.

Design and Method:

The peptide, seven-amino-acid sequence from second extracellular loop of rat AT1R was synthesized and then conjugated with pneumococcal surface protein A (PspA) as a carrier protein for the nasal vaccination. 10 ug of AT1R-PspA antigen was mixed with cyclic di-GMP adjuvant to increase its immunogenicity and incorporated into cationic nanometer-sized hydrogel (nanogel) for the effective delivery to the nasal epithelium where was negatively charged. Male spontaneously hypertensive rats (SHRs) (n = 10/group) were treated transiently with five nasal administration of vehicle (cyclic di-GMP and nanogel alone) or AT1R-PspA vaccine at age 4, 5, 6, 7 and 8 weeks, and measured their blood pressures, AT1R-specific serum IgG antibody titers and plasma angiotensin II concentration.

Results:

In the preliminary study, nasal immunization with AT1R-PspA (10 ug × 5 times) induced anti-AT1R serum IgG antibodies at the same level as subcutaneous vaccination (20 ug × 3 times). Nasal vaccination of AT1R-PspA also caused a sustained decrease in systolic blood pressure in SHRs (vehicle group 224.1 mmHg vs vaccine group 205.1 mmHg, at 10 weeks after the last vaccination, n = 10/group, p < 0.01). Plasma angiotensin II was increased by the vaccination, but the difference was not significant (vehicle 6.30 pg/ml vs vaccine 23.64 pg/ml, n = 5/group, p = 0.2614).

Conclusions:

These results suggest that the nasal vaccination of AT1R-PspA may be effective for the attenuation of hypertension without injection-associated pain and local skin adverse events.

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