AJP001, a novel helper T‐cell epitope, induces a humoral immune response with activation of innate immunity when included in a peptide vaccine

摘要

Abstract Vaccine design requires well‐tailored formulations including a T‐cell epitope and adjuvants. We identified a novel cationic peptide, AJP001, which possesses a strong affinity for murine MHC class II alleles (H2‐IEd and H2‐IAd) and low affinity for H2‐IAb. We designed an AJP001 and epitope peptide‐conjugated vaccine, AJP001‐angiotensin (Ang) II, which was intracutaneously administered to mice three times at 2‐week intervals. Indeed, the AJP001‐Ang II vaccine induced antibody production against Ang II in BALB/cA mice but not in C57BL/6 mice. To estimate the T‐cell‐dependent immunogenicity of the AJP001 conjugate vaccine in human cells, naïve human peripheral blood mononuclear cells (PBMCs) were exposed to AJP001‐Ang II, and T‐cell proliferation was evaluated by analyzing cell division using flow cytometric measurement of carboxyfluorescein succinimidyl ester (CFSE) dye dilution. To activate the immune response, the innate immune system must be activated by adjuvant treatment. Interestingly, treatment with AJP001 induced IL‐1β and IL‐18 secretion via NLRP3 inflammasome activation and induced TNF‐α and IL‐6 production through an NF‐κB‐dependent pathway in human and mouse macrophages. These results suggest that AJP001 behaves as a T‐cell epitope in mice and humans and is a useful tool for the formulation of peptide vaccines without the addition of adjuvants.