Administration of anti-CTLA-4 monoclonal antibody augments protective immunity induced by Schistosoma japonicum glutathione-S-transferase

Parasite Immunol. 2019 Aug;41(8):e12657. doi: 10.1111/pim.12657. Epub 2019 Jun 17.

Abstract

Aims: The aim of this study was to evaluate the effect of anti-CTLA-4 monoclonal antibody (mAb) on 26-kDa glutathione-S-transferase (GST) vaccine-induced immunity against Schistosoma japonicum infection.

Methods and results: Mice immunized with GST before infection with S japonicum cercariae were injected with anti-CTLA-4 mAb. Worm reduction rate of GST was increased from 25.41% in mice with GST immunization to 52.48% in mice with GST plus anti-CTLA-4 mAb. The percentages of regulatory T cells (Tregs) were significantly higher following administration of both GST and anti-CTLA-4 mAb, or anti-CTLA-4 mAb alone. Elevated levels of IFN-γ, IL-2, IL-4 and IL-5 were observed.

Conclusion: These results demonstrated that CTLA-4 may inhibit the protective effect of GST vaccine, and anti-CTLA-4 mAb may be used as an adjuvant to enhance the immune protection conferred by the GST vaccine by enhancing Th1- and Th2-type immune response.

Keywords: Schistosoma japonicum; cytotoxic T-lymphocyte antigen-4; glutathione-S-transferase; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology*
  • CTLA-4 Antigen / immunology*
  • Female
  • Glutathione Transferase / administration & dosage
  • Glutathione Transferase / genetics
  • Glutathione Transferase / immunology*
  • Humans
  • Immunization
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Schistosoma japonicum / enzymology*
  • Schistosoma japonicum / genetics
  • Schistosoma japonicum / immunology
  • Schistosomiasis japonica / immunology
  • Schistosomiasis japonica / parasitology
  • Schistosomiasis japonica / prevention & control*
  • T-Lymphocytes, Regulatory / immunology
  • Vaccines / administration & dosage
  • Vaccines / genetics
  • Vaccines / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Monoclonal
  • CTLA-4 Antigen
  • Interleukin-2
  • Vaccines
  • Interleukin-4
  • Glutathione Transferase