SpeS: A Novel Superantigen and Its Potential as a Vaccine Adjuvant against Strangles.
Abstract: Bacterial superantigens (sAgs) are powerful activators of the immune response that trigger unspecific T cell responses accompanied by the release of proinflammatory cytokines. () and () produce sAgs that play an important role in their ability to cause disease. Strangles, caused by , is one of the most common infectious diseases of horses worldwide. Here, we report the identification of a new sAg of , 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 to six 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 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-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.
Publication Date: 2020-06-23 PubMed ID: 32586031PubMed Central: PMC7352279DOI: 10.3390/ijms21124467Google Scholar: Lookup
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- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article is about a new superantigen identified in bacteria that cause Strangles in horses, and how its mutated form can potentially be used as a vaccine adjuvant to improve immune response.
Key Findings
- The study identifies a new superantigen, labeled as SpeS, present in the bacteria causing Strangles, a common infectious disease in horses. Superantigens are a category of antigens that activate the immune response by triggering T cells.
- The researchers found that the mutation of the T cell receptor (TCR) binding motif of the superantigen resulted in losing its TCR-binding capability, while its interaction with major histocompatibility complex (MHC) class II molecules was retained.
Research Methodology
- The researchers conducted a process known as fusion with SpeS and its mutated form to six surface proteins, using two different peptide linkers, to verify if MHC class II-binding properties were retained.
- They utilized proliferation assays, qPCR, and flow cytometry analysis to gauge the results. The data analysis presented that SpeS and its fusion proteins induced less mitogenic activity and interferon gamma expression when compared to the non-mutated form.
- The mutated SpeS still had effective Antigen-Presenting Cell (APC) binding properties.
Implications of the Study
- The results suggest that the fusion of SpeS mutant proteins could be used to direct vaccine antigens toward antigen-presenting cells in vivo. This strategy has the potential to enhance antigen presentation and subsequently improve immune responses.
- However, future studies would be necessary to verify this application and to develop a practical approach to using SpeS superantigen as a vaccine adjuvant against Strangles.
Cite This Article
APA
Dominguez-Medina CC, Rash NL, Robillard S, Robinson C, Efstratiou A, Broughton K, Parkhill J, Holden MTG, Lopez-Alvarez MR, Paillot R, Waller AS.
(2020).
SpeS: A Novel Superantigen and Its Potential as a Vaccine Adjuvant against Strangles.
Int J Mol Sci, 21(12), 4467.
https://doi.org/10.3390/ijms21124467 Publication
Researcher Affiliations
- Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK.
- Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK.
- Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK.
- Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK.
- Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
- Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
- Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
- Department of Veterinary Medicine, University of Cambridge Veterinary School, Cambridge CB3 0ES, UK.
- Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
- School of Medicine, University of St Andrews, St Andrews KY16 9TF, UK.
- Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK.
- Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK.
- LABÉO Frank Duncombe, 1 Route de Rosel, CEDEX 4, 14053 Caen, France.
- Biotargen, Normandie Univ, UniCaen, 3 rue Nelson Mandela, 14280 Saint-Contest, France.
- Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK.
MeSH Terms
- Adjuvants, Immunologic / chemistry
- Antigen Presentation / immunology
- Bacterial Proteins / immunology
- Exotoxins / immunology
- Histocompatibility Antigens Class II / immunology
- Humans
- Membrane Proteins / immunology
- Membrane Proteins / metabolism
- Meningitis
- Phylogeny
- Receptors, Antigen, T-Cell / metabolism
- Streptococcal Infections / immunology
- Streptococcal Infections / microbiology
- Streptococcal Infections / prevention & control
- Streptococcus equi / immunology
- Streptococcus equi / isolation & purification
- Superantigens / immunology
- Vaccines / administration & dosage
- Vaccines / immunology
Grant Funding
- BB/P002757/1 / Biotechnology and Biological Sciences Research Council
Conflict of Interest Statement
The authors declare no competing interests.
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Citations
This article has been cited 2 times.- Martin KH, Redding LE, Boyle AG. Factors Influencing Veterinarian Opinion on Reporting of Equine Strangles in the United States. J Equine Vet Sci 2022 Jul;114:103947.
- Soliman R, Yousef M, Gelil SA, Aboul-Ella H. Development of novel Streptococcus equi vaccines with an assessment of their immunizing potentials and protective efficacies. BMC Vet Res 2024 May 3;20(1):173.
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