Objective:Therapeutic vaccines with biological targeting effects have great potential in the cardio-vascular diseases therapy.The viral like particle-based vaccine ATRQβ-001 targeting angiotensin Ⅱ receptor type 1(AT1R)has shown effective anti-hypertensive and target organ protective effects in various hypertension animal models.To further improve the immune efficiency,aluminum hydroxide adjuvant is used in vaccine preparation.The purpose of this study is to evaluate the immunological responses and safety of HJY-ATRQβ-001 vaccine prep-arations with different concentrations of aluminum hydroxide,aiming to guide the proper application of the adju-vant.Methods:HJY-ATRQβ-001 was mixed with different concentrations of aluminum hydroxide to produce vac-cine preparation 1(containing 1 mg/mL aluminum hydroxide)and vaccine preparation 2(containing 2 mg/mL a-luminum hydroxide).Differential immune responses induced by the vaccine preparations were evaluated through immunofluorescence,flow cytometry,enzyme-linked immunosorbent assay and enzyme-linked immunospot assay.Results:Following subcutaneous immunization,HJY-ATRQβ-001 entered the subcapsular area of the draining lymph nodes and gradually deposited on the surface of follicular dendritic cells(FDCs),providing continuous anti-gen stimulation to follicular B cells.Meanwhile,both vaccine preparations effectively induced the maturation of antigen presenting cells(DCs)and T cell activation dominated by T helper 2 cells(Th2)and follicular helper T cells(Tfh).Notably,vaccine preparation 2 simultaneously activated Th17,cytotoxic T cells(CTLs)and regula-tory T cells(Treg),showing stronger T cell stimulation,although these T cells activation was not sustained.Vaccine deposition and helper T cells activation promoted efficient humoral immune responses,manifested as spe-cific antibody secreting cells,specific antibodies,and B cell memory formation against AT1R peptide segment.However,there was no significant differences in humoral immunity activation between the two groups of vaccine preparations containing different concentrations of aluminum adjuvant.Conclusion:HJY-ATRQβ-001 vaccine adju-vanted with aluminum hydroxide performed great immunological effects,while increasing the concentration of the adjuvant did not improve the humoral immunity effects but augmented the immune stimulation.To balance the immunological effects and safety,the addition of the adjuvant and proper dosage should be carefully deliberated during vaccine preparation.
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