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Towards a vaccine against rheumatic fever
1School of Medicine, Heart Institute (InCor), University of São Paulo, São Paulo, Brazil. luizagui@usp.br
Insights
Researchers identified key T and B cell epitopes from Streptococcus pyogenes M protein. These findings offer potential for developing a vaccine against rheumatic fever and rheumatic heart disease.
Area of Science:
- Immunology
- Infectious Diseases
- Cardiovascular Medicine
Background:
- Rheumatic fever (RF) is a significant autoimmune disease affecting millions globally, primarily children in developing nations.
- It stems from Streptococcus pyogenes throat infections and can lead to chronic rheumatic heart disease (RHD) with permanent valvular damage.
- Understanding the autoimmune mechanisms driving RF/RHD is crucial for developing preventative strategies.
Purpose of the Study:
- To investigate the cellular and molecular pathogenesis of rheumatic heart disease.
- To identify protective T and B cell epitopes from the M protein of Streptococcus pyogenes.
- To lay the groundwork for a potential vaccine against this post-infection autoimmune disease.
Main Methods:
- Analyzed 620 human blood samples against overlapping peptides from the M protein's C-terminal portion.
- Focused on identifying specific T and B cell epitopes involved in the autoimmune response.
- Utilized in vitro assays to assess the functional impact of identified epitopes.
Main Results:
- Identified distinct T and B cell epitopes (22 and 25 amino acids, respectively) within the M protein.
- Discovered a conserved 16-amino acid core shared by both T and B cell epitopes.
- Antibodies targeting the B cell epitope demonstrated inhibition of bacterial invasion and adhesion in vitro.
Conclusions:
- The identified T and B cell epitopes show promise as targets for a vaccine against Streptococcus pyogenes.
- These findings contribute to a deeper understanding of RHD pathogenesis.
- Further development could lead to effective prevention of RF/RHD, particularly in high-risk populations.
Abstract:
Rheumatic fever (RF) is an autoimmune disease which affects more than 20 million children in developing countries. It is triggered by Streptococcus pyogenes throat infection in untreated susceptible individuals. Carditis, the most serious manifestation of the disease, leads to severe and permanent valvular lesions, causing chronic rheumatic heart disease (RHD). We have been studying the mechanisms leading to pathological autoimmunity in RF/RHD for the last 15 years. Our studies allowed us a better understanding of the cellular and molecular pathogenesis of RHD, paving the way for the development of a safe vaccine for a post-infection autoimmune disease. We have focused on the search for protective T and B cell epitopes by testing 620 human blood samples against overlapping peptides spanning 99 residues of the C-terminal portion of the M protein, differing by one amino acid residue. We identified T and B cell epitopes with 22 and 25 amino acid residues, respectively. Although these epitopes were from different regions of the C-terminal portion of the M protein, they showed an identical core of 16 amino acid residues. Antibodies against the B cell epitope inhibited bacterial invasion/adhesion in vitro. Our results strongly indicated that the selected T and B cell epitopes could potentially be protective against S. pyogenes.
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