Abstract
We developed a virus-like particle (VLP)-based therapeutic vaccine against angiotensin II receptor type 1, ATR-AP205-001, which could significantly reduce the blood pressure and protect target organs of hypertensive animals. In this study, we focused on the immunological effect and safety of the VLP-based vaccine. By comparing to the depolymerized dimeric vaccine ATR-Dimer-001, we found that ATR-AP205-001 reached subcapsular sinus of lymph node shortly after administration, followed by accumulation on follicle dendritic cells via follicle B cell transportation, while ATR-Dimer-001 vaccine showed no association with FDCs. ATR-AP205-001 vaccine strongly activated dendritic cells, which promoted T cells differentiation to follicular helper T cells. ATR-AP205-001 vaccine induced powerful germinal center reaction, which was translated to a boost of specific antibody production and long-lasting B cell memory, far superior to ATR-Dimer-001 vaccine. Moreover, neither cytotoxic T cells, nor Th1/Th17 cell-mediated inflammation was observed in ATR-AP205-001 vaccine, similar to ATR-Dimer-001 vaccine. We concluded that ATR-AP205-001 vaccine quickly induced potent humoral immunity through collaboration of B cells, follicular dendritic cells and follicular helper T cells, providing an effective and safe intervention for hypertension in the future clinical application.
Highlights
We developed a virus-like particle (VLP)-based therapeutic vaccine against angiotensin II receptor type 1, ATR-AP205-001, which could significantly reduce the blood pressure and protect target organs of hypertensive animals
To accelerate the clinical transformation of AT1R-VLP vaccine, we further explored immune response mechanism of the novel ATR-AP205-001 vaccine
It was found that ATR-AP205-001 vaccine quickly induced potent humoral immunity through collaboration of B cells, follicular dendritic cells and follicular helper T cells
Summary
We developed a virus-like particle (VLP)-based therapeutic vaccine against angiotensin II receptor type 1, ATR-AP205-001, which could significantly reduce the blood pressure and protect target organs of hypertensive animals. Our team invented a virus-like particle (VLP)-based anti-hypertensive vaccine against AT1R, which could significantly lower the blood pressure and protect target organs of hypertensive animals[4], even ameliorate atherosclerosis[5] and nephropathy[6] in animal models. The half life (14.4 days) of productive antibody is much longer than existing anti-hypertensive chemical drugs[4], which indicates AT1R-VLP vaccine reduces blood pressure more steadily. Obvious RAS feedback activation which makes the effect of ARBs somewhat self-limiting was not found in vaccinated animals[6,7] All these advantages support that AT1R-VLP vaccine is a novel and promising intervention to hypertension. Conjugation of ATR001 with AP205 VLP carrier (designated ATR-AP205-001) should be an entirely feasible strategy to overcome self-tolerance of ATR001 and achieve ideal humoral immune response
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