Spes: A novel superantigen and its potential as a vaccine adjuvant against strangles

C. Coral Dominguez-Medina, Nicola L. Rash, Sylvain Robillard, Carl Robinson, Androulla Efstratiou, Karen Broughton, Julian Parkhill, Matthew T.G. Holden, Maria R. Lopez-Alvarez, Romain Paillot, Andrew S. Waller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Bacterial superantigens (sAgs) are powerful activators of the immune response that trigger unspecific T cell responses accompanied by the release of proinflammatory cytokines. Streptococcus equi (S. equi) and Streptococcus zooepidemicus (S. zooepidemicus) produce sAgs that play an important role in their ability to cause disease. Strangles, caused by S. equi, is one of the most common infectious diseases of horses worldwide. Here, we report the identification of a new sAg of S. zooepidemicus, SpeS, and show that mutation of the putative T cell receptor (TCR)-binding motif (YAY to IAY) abrogated TCR-binding, whilst maintaining interaction with major histocompatibility complex (MHC) class II molecules. The fusion of SpeS and SpeSY39I to six S. equi surface proteins using two different peptide linkers was conducted to determine if MHC class II-binding properties were maintained. Proliferation assays, qPCR and flow cytometry analysis showed that SpeSY39I and its fusion proteins induced less mitogenic activity and interferon gamma expression when compared to SpeS, whilst retaining Antigen-Presenting Cell (APC)-binding properties. Our data suggest that SpeSY39I-surface protein fusions could be used to direct vaccine antigens towards antigen-presenting cells in vivo with the potential to enhance antigen presentation and improve immune responses.

Original languageEnglish
Article number4467
JournalInternational Journal of Molecular Sciences
Volume21
Issue number12
DOIs
Publication statusPublished - 23 Jun 2020

Bibliographical note

Funding Information: This research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/P002757/1, March 2017 to June 2020).

Open Access: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Publisher Copyright:© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Citation: Dominguez-Medina, C.C.; Rash, N.L.; Robillard, S.; Robinson, C.; Efstratiou, A.; Broughton, K.; Parkhill, J.; Holden, M.T.G.; Lopez-Alvarez, M.R.; Paillot, R.; Waller, A.S. SpeS: A Novel Superantigen and Its Potential as a Vaccine Adjuvant against Strangles. Int. J. Mol. Sci. 2020, 21, 4467.

DOI: https://doi.org/10.3390/ijms21124467

Keywords

  • Adjuvant
  • Horse
  • Immune response
  • Strangles
  • Streptococcus equi
  • Streptococcus zooepidemicus
  • Superantigen
  • Vaccine

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