A novel angiotensin II peptide vaccine without an adjuvant inmice

Abstract

Objectives: We recently developed a novel peptide, AJP001, that possesses both a mouse T-cell epitope and adjuvant action. Direct conjugation to the antigen is useful for peptide vaccines without the addition of adjuvants. In this study, the efficacy of an angiotensin (Ang) II and AJP001-conjugated peptide vaccine (AJ-Ang II) was evaluated in mice. Methods: The anti-Ang II antibody titer was measured in Balb/C mice following three injections of AJ-Ang II at 2- week intervals. SBP was measured during vaccination of Balb/C mice treated with Ang II infusion (1mg/kg per min). Results: AJ-Ang II treatment resulted in an increase in the anti-Ang II antibody titer in a dose-dependent manner without the addition of adjuvants. In the analysis of the humoral immune response, AJ-Ang II mainly elicited IgG1 antibodies and IL-4 and IL-10 production, as measured by an enzyme-linked immune absorbent spot assay, which suggests the induction of a Th2 response. Importantly, cotreatment with purified antibodies attenuated Ang IIinduced extracellular signal-regulated kinase phosphorylation and nuclear factor (NF)-kB activation in cultured vascular smooth muscle cells. The SBP in immunized mice was significantly lower than that in nonimmunized mice (135.9_8.5 vs. 154.9_16.8 mmHg, P 0.02). Furthermore, Ang II-induced perivascular fibrosis in the heart was significantly attenuated in immunized mice, which also exhibited decreased mRNA expression of collagen I/III and transforming growth factor-b. Conclusion: AJ-Ang II may be a simple and useful therapeutic peptide vaccine without the addition of any adjuvants.