Combined vaccines against angiotensin II receptor type 1 and alpha 1D-adrenergic receptor for hypertension

Abstract

Purpose: Compared with monotherapy, combination therapy with multiple antihypertensive drugs has demonstrated superior efficacy in the management of hypertension. The aim of this study was to explore the efficacy of multitarget combined vaccines in achieving simultaneous antihypertensive and target organ protection effects. Methods: Our team has developed ATRQβ-001 and ADRQβ-004 vaccines targeting Ang II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR), respectively. In NG-nitroarginine methyl ester (l-NAME) + abilities spontaneously hypertensive rats (SHRs) model, SHRs were simultaneously inoculated with ATRQβ-001 and ADRQβ-004 vaccines. Histological and biochemical analyses were performed to evaluate the antihypertensive effects and target organ protection of the ATRQβ-001 and ADRQβ-004 combined vaccines in comparison with those of the single vaccine. Results: Both ATRQβ-001 and ADRQβ-004 vaccines induced robust antibody production, resulting in persistent high antibody titers in rats. Notably, the combined administration of both vaccines significantly decreased SBP in SHRs compared with treatment with a single vaccine, both before and after l-NAME administration. Furthermore, the combined vaccine regimen demonstrated superior efficacy in protecting against vascular remodeling, myocardial hypertrophy and fibrosis, and kidney injury in SHRs. Mechanistically, the combined vaccines exhibited significantly downregulated the expression of angiotensin II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR). Importantly, no apparent immune-related adverse effects were observed in animals immunized with the combined vaccines. Conclusion: Preliminary findings from this investigation suggest that co-administration of the novel ATRQβ-001 and ADRQβ-004 vaccines holds potential as a groundbreaking therapeutic strategy for managing hypertension.