An IL-17 peptide-based and virus-like particle vaccine enhances the bioactivity of IL-17 in vitro and in vivo

Abstract

Aims: To develop an IL-17 peptide-based virus-like particle vaccine that elicits autoantibodies to IL-17 and to evaluate the effects of the vaccine in mice with experimental colitis. Materials & methods: Recombinant IL-17 vaccines were constructed by inserting selected peptides derived from mouse IL-17 into the carrier protein, hepatitis B core antigen, using molecular engineering methods. To evaluate the in vivo effects of the vaccine, mice with 2,4,6-trinitrobenzene sulfonic acid-induced chronic colitis were injected three times with the vaccine, carrier or saline after the second delivery of 2,4,6-trinitrobenzene sulfonic acid. Colon inflammation and fibrosis were evaluated by histological examination. Serum IL-17-specific IgG and colon-tissue cytokine levels were measured by ELISA. In vitro inhibition tests of sera from vaccine-immunized mice were performed using IL-17-induced IL-6 production by NIH 3T3 cells and IL-17-induced TNF production by macrophages. Results: Immunization with the vaccine without the use of adjuvants induced high-titered and long-lasting antibodies to IL-17. Unexpectedly, vaccinated mice exhibited increases in colon inflammation, collagen deposition, levels of TNF and IL-17 cytokines compared with carrier and saline groups. Furthermore, in vitro study revealed that serum IL-17-specific IgG from vaccine-immunized mice significantly enhanced IL-17-induced IL-6 production and IL-17-induced TNF production dose-dependently. Conclusion: The IL-17 peptide-based vaccine enhances the bioactivity of IL-17 in vitro and in vivo, providing a potential immunotherapy for treatment of diseases associated with insufficient IL-17 production, such as hyper-IgE syndrome.