Peptide-based vaccine targeting IL17A attenuates experimental spondyloarthritis in HLA-B27 transgenic rats

RMD Open. 2023 Feb;9(1):e002851. doi: 10.1136/rmdopen-2022-002851.

Abstract

Objectives: Spondyloarthritis (SpA) is known as series of immune-mediated inflammatory disease of the axial and peripheral joints. Human leucocyte antigen (HLA)-B27 is a genetic risk factor for SpA. Recent evidence suggests that the interleukin -17 (IL17) axis strongly contributes to SpA. This study aimed to assess the efficacy of an IL17A peptide-based vaccine on SpA manifestations in model rats.

Methods: HLA-B27/human β2-microglobulin (hβ2M) transgenic rats were immunised with heat-inactivated Mycobacterium tuberculosis (MT) to develop spondylitis and arthritis as an experimental SpA model after immunisation with a keyhole limpet hemocyanin-conjugated IL17A peptide-based vaccine with an alum adjuvant three times. The IL17A antibody titre was assessed using ELISA, and arthritis score and joint thickness were monitored two times a week. Enzyme-linked immunospot (ELISpot) assays for IL4- and interferon-γ-secreting splenocytes were conducted to evaluate IL17A-specific T cell activation. We also evaluated the effect of IL17A vaccine in SpA therapeutic model.

Results: The IL17A peptide-based vaccine with alum adjuvant successfully induced antibody production and suppressed the arthritis score and joint thickness. X-ray and histological analyses showed that enthesitis, bone destruction and new bone formation were inhibited by the IL17A vaccine. The ELISpot assay showed that the IL17A peptide-based vaccine did not elicit any IL17A-reactive T cell responses. IL17A vaccine tends to mitigate, but not significant, in SpA treatment model. These data showed that the peptide-based vaccine targeting IL17A alleviated the SpA phenotype in a heat-inactivated MT-induced SpA model in HLA-B27/hβ2M transgenic rats.

Conclusions: IL17A peptide-based vaccine may be a therapeutic option for SpA treatment.

Keywords: Autoimmunity; Spondylitis, Ankylosing; Vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alum Compounds / therapeutic use
  • Animals
  • HLA-B27 Antigen* / genetics
  • Humans
  • Interleukin-17
  • Rats
  • Rats, Transgenic
  • Spondylarthritis* / drug therapy

Substances

  • aluminum sulfate
  • HLA-B27 Antigen
  • Alum Compounds
  • IL17A protein, human
  • Interleukin-17