Hypertension remains the most important modifiable risk factor for cardiovascular disease (CVD) morbidity and mortality. Despite availability of good therapeutic interventions for controlling high blood pressure (BP), the global treatment and control rates remain poor. One of the key factors is poor adherence to daily dosing of antihypertensive medication in long term. Patients with long standing sub-optimal BP control develop end-organ damage such as left ventricular hypertrophy (LVH), proteinuria and adverse vascular modelling besides having worse CVD outcomes.

The results from this dual vaccine animal study targeting AT1R and α1D-AR show promising results with a significantly greater BP reduction compared with the monotherapy groups. The combined vaccines also demonstrated benefit with vascular remodelling, cardiac hypertrophy, fibrosis and renal injury that are all desirable attributes with a successful novel therapy. It also shows downregulation of the expression of AT1R and α1D-AR with no evidence of immune damage. There is growing evidence of sympathetic stimulation with the renin angiotensin aldosterone system (RAAS) and the ATRQβ-001 vaccine significantly reduced the activation of circulating norepinephrine and catecholamine levels.

All these added benefits could help reduce end-organ damage and help achieve better outcomes in hypertension cohorts. These animal study data are supportive of further development of these dual vaccines as novel therapies for hypertension in humans. Depending upon frequency of dosing, they could also help alleviate the poor adherence issue with daily dosing hypertension therapies. But development of novel therapies for hypertension in humans comes with its own challenges.

It is well-recognized that hypertension is multifactorial and no one therapy works for all phenotypes of hypertension (mild vs. resistant; isolated systolic vs. systo-diastolic; low renin vs. high renin; different age and ethnicities). We need robust evaluation of not just on target but also off target effects in short and long term to demonstrate efficacy and safety of any novel therapy. Response with vaccines and antibodies could be diminished with time due to development of autoantibodies and it depends upon humanization of these therapies. Increasing BP could be a lifesaving response in certain emergencies such as sepsis and acute bleeding. It needs to be shown how the effect of such long-acting vaccines could be terminated in a case of emergency.