SpeS: A Novel Superantigen and Its Potential as a Vaccine Adjuvant against Strangles
Bacterial superantigens (sAgs) are powerful activators of the immune response that trigger unspecific T cell responses accompanied by the release of proinflammatory cytokines. <i>Streptococcus equi</i> (<i>S. equi</i>) and <i>Streptococcus zooepidemicus</i> (<i...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/12/4467 |
| Summary: | Bacterial superantigens (sAgs) are powerful activators of the immune response that trigger unspecific T cell responses accompanied by the release of proinflammatory cytokines. <i>Streptococcus equi</i> (<i>S. equi</i>) and <i>Streptococcus zooepidemicus</i> (<i>S. zooepidemicus</i>) produce sAgs that play an important role in their ability to cause disease. Strangles, caused by <i>S. equi</i>, is one of the most common infectious diseases of horses worldwide. Here, we report the identification of a new sAg of <i>S. zooepidemicus</i>, 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 SpeS<sup>Y39I</sup> to six <i>S. equi</i> 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 SpeS<sup>Y39I</sup> 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 SpeS<sup>Y39I</sup>-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. |
|---|---|
| ISSN: | 1661-6596 1422-0067 |