Streptococcus pyogenes vaccine candidates do not induce autoimmune responses in a rheumatic heart disease model
Abstract We have developed a candidate vaccine to protect against multiple strains of Streptococcus pyogenes infections. The candidate vaccine contains two synthetic peptides derived from S. pyogenes proteins: the M-protein epitope, p*17 and the IL-8 degrading S. pyogenes Cell-Envelope Proteinase (S...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-02-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-023-00604-2 |
| _version_ | 1797641589386903552 |
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| author | Simone Reynolds Rukshan Ahamed Mohamed Rafeek Adam Hamlin Ailin Lepletier Manisha Pandey Natkunam Ketheesan Michael F. Good |
| author_facet | Simone Reynolds Rukshan Ahamed Mohamed Rafeek Adam Hamlin Ailin Lepletier Manisha Pandey Natkunam Ketheesan Michael F. Good |
| author_sort | Simone Reynolds |
| collection | DOAJ |
| description | Abstract We have developed a candidate vaccine to protect against multiple strains of Streptococcus pyogenes infections. The candidate vaccine contains two synthetic peptides derived from S. pyogenes proteins: the M-protein epitope, p*17 and the IL-8 degrading S. pyogenes Cell-Envelope Proteinase (SpyCEP) epitope, K4S2. In this study we utilise a rat autoimmune valvulitis model that displays both the cardiac and neurobehavioural pathology associated with post-streptococcal sequelae, to assess if the vaccine candidate antigens induce autoimmune complications and inflammatory pathology. Each antigen was conjugated to carrier protein diphtheria toxoid (DT) and independently assessed for potential to induce autoimmune pathology in female Lewis rats. Rats were administered three subcutaneous doses, and one intranasal dose over a four-week study with a two-week recovery period. A positive control group received recombinant S. pyogenes M5 (rM5) protein, and the negative control group received PBS. Rats that received rM5 developed significant cardiac and neurological pathologies. There was no evidence of these pathologies in the PBS control group, or the rats administered either P*17-DT or K4S2-DT. This study provides further preclinical evidence of the safety of the vaccine candidates p*17 and K4S2 and their appropriateness as candidates in human clinical trials. |
| first_indexed | 2024-03-11T13:47:51Z |
| format | Article |
| id | doaj.art-0306dd7ec4e845928dcb77cf5b8d90f3 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-11T13:47:51Z |
| publishDate | 2023-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-0306dd7ec4e845928dcb77cf5b8d90f32023-11-02T09:44:16ZengNature Portfolionpj Vaccines2059-01052023-02-018111010.1038/s41541-023-00604-2Streptococcus pyogenes vaccine candidates do not induce autoimmune responses in a rheumatic heart disease modelSimone Reynolds0Rukshan Ahamed Mohamed Rafeek1Adam Hamlin2Ailin Lepletier3Manisha Pandey4Natkunam Ketheesan5Michael F. Good6Institute for Glycomics, Griffith UniversitySchool of Science & Technology, University of New EnglandSchool of Science & Technology, University of New EnglandInstitute for Glycomics, Griffith UniversityInstitute for Glycomics, Griffith UniversityInstitute for Glycomics, Griffith UniversityInstitute for Glycomics, Griffith UniversityAbstract We have developed a candidate vaccine to protect against multiple strains of Streptococcus pyogenes infections. The candidate vaccine contains two synthetic peptides derived from S. pyogenes proteins: the M-protein epitope, p*17 and the IL-8 degrading S. pyogenes Cell-Envelope Proteinase (SpyCEP) epitope, K4S2. In this study we utilise a rat autoimmune valvulitis model that displays both the cardiac and neurobehavioural pathology associated with post-streptococcal sequelae, to assess if the vaccine candidate antigens induce autoimmune complications and inflammatory pathology. Each antigen was conjugated to carrier protein diphtheria toxoid (DT) and independently assessed for potential to induce autoimmune pathology in female Lewis rats. Rats were administered three subcutaneous doses, and one intranasal dose over a four-week study with a two-week recovery period. A positive control group received recombinant S. pyogenes M5 (rM5) protein, and the negative control group received PBS. Rats that received rM5 developed significant cardiac and neurological pathologies. There was no evidence of these pathologies in the PBS control group, or the rats administered either P*17-DT or K4S2-DT. This study provides further preclinical evidence of the safety of the vaccine candidates p*17 and K4S2 and their appropriateness as candidates in human clinical trials.https://doi.org/10.1038/s41541-023-00604-2 |
| spellingShingle | Simone Reynolds Rukshan Ahamed Mohamed Rafeek Adam Hamlin Ailin Lepletier Manisha Pandey Natkunam Ketheesan Michael F. Good Streptococcus pyogenes vaccine candidates do not induce autoimmune responses in a rheumatic heart disease model npj Vaccines |
| title | Streptococcus pyogenes vaccine candidates do not induce autoimmune responses in a rheumatic heart disease model |
| title_full | Streptococcus pyogenes vaccine candidates do not induce autoimmune responses in a rheumatic heart disease model |
| title_fullStr | Streptococcus pyogenes vaccine candidates do not induce autoimmune responses in a rheumatic heart disease model |
| title_full_unstemmed | Streptococcus pyogenes vaccine candidates do not induce autoimmune responses in a rheumatic heart disease model |
| title_short | Streptococcus pyogenes vaccine candidates do not induce autoimmune responses in a rheumatic heart disease model |
| title_sort | streptococcus pyogenes vaccine candidates do not induce autoimmune responses in a rheumatic heart disease model |
| url | https://doi.org/10.1038/s41541-023-00604-2 |
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