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A vaccine against Streptococcus pyogenes: the potential to prevent rheumatic fever and rheumatic heart disease
Luiza Guilherme1, Frederico Moraes Ferreira, Karen Francine Köhler
1Heart Institute (InCor), Laboratory of Immunology, University of São Paulo, São Paulo, Brazil. luizagui@usp.br
Insights
A novel vaccine candidate peptide, StreptInCor, targeting Streptococcus pyogenes, demonstrates immunogenicity and safety in extensive animal model testing. This peptide shows promise for a universal vaccine against S. pyogenes infections.
Area of Science:
- Microbiology
- Vaccinology
- Immunology
Background:
- Streptococcus pyogenes is a significant pathogen causing severe invasive infections and sequelae like acute rheumatic fever and rheumatic heart disease.
- Developing an effective vaccine against S. pyogenes has been a long-standing challenge, with various approaches explored over decades.
Purpose of the Study:
- To summarize 5 years of research on the immunogenicity and safety of a novel vaccine candidate peptide, StreptInCor.
- To evaluate StreptInCor's potential as a universal vaccine epitope targeting S. pyogenes.
Main Methods:
- Development of the StreptInCor peptide from the M protein's C-terminal portion, containing T- and B-cell epitopes.
- Assessment of immunogenicity via cellular and humoral immune responses in individuals with diverse HLA class II molecules.
- Structural elucidation using nuclear magnetic resonance spectroscopy and stability evaluation via circular dichroism.
- Safety and immunogenicity testing in inbred, outbred, and HLA class II transgenic mouse models.
Main Results:
- StreptInCor overlapping peptides induced robust cellular and humoral immune responses across different HLA class II backgrounds, suggesting universal epitope potential.
- Nuclear magnetic resonance revealed a distinct structure for StreptInCor, comprising two microdomains linked by an alpha-helix.
- Circular dichroism confirmed the peptide's structural stability under various physicochemical conditions.
- Extensive animal studies showed no deleterious or autoimmune reactions, even after prolonged vaccination periods.
Conclusions:
- The StreptInCor peptide candidate is immunogenic and safe, demonstrating potential for a universal vaccine against Streptococcus pyogenes.
- The elucidated structure and demonstrated stability contribute to understanding its vaccine potential.
- Further development of StreptInCor could lead to a crucial tool for preventing S. pyogenes-related diseases.
Abstract:
Streptococcus pyogenes causes severe, invasive infections such as the sequelae associated with acute rheumatic fever, rheumatic heart disease, acute glomerulonephritis, uncomplicated pharyngitis, and pyoderma. Efforts to produce a vaccine against S. pyogenes began several decades ago, and different models have been proposed. We have developed a vaccine candidate peptide, StreptInCor, comprising 55 amino acid residues of the C-terminal portion of the M protein and encompassing both the T- and B-cell protective epitopes. The present article summarizes data from the previous 5 years during which we tested the immunogenicity and safety of StreptInCor in different animal models. We showed that StreptInCor overlapping peptides induced cellular and humoral immune responses of individuals bearing different HLA class II molecules. These results are consistent with peptides that have a universal vaccine epitope. The tridimensional molecular structure of StreptInCor was elucidated by nuclear magnetic resonance spectroscopy, which showed that its structure is composed of two microdomains linked by an 18-residue α-helix. Additionally, we comprehensively evaluated the structural stability of the StreptInCor peptide in different physicochemical conditions using circular dichroism. Additional experiments were performed with inbred, outbred, and HLA class II transgenic mice. Analysis of several organs of these mice showed neither deleterious nor autoimmune reactions even after a long period of vaccination, indicating that the StreptInCor candidate peptide could be considered as an immunogenic and safe vaccine.
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