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StreptInCor: a candidate vaccine epitope against S. pyogenes infections induces protection in outbred mice
Edilberto Postol1, Raquel Alencar, Fabio T Higa
1Heart Institute, School of Medicine, University of São Paulo, São Paulo, Brazil.
Abstract:
Infection with Streptococcus pyogenes (S. pyogenes) can result in several diseases, particularly in children. S. pyogenes M protein is the major virulence factor, and certain regions of its N-terminus can trigger autoimmune sequelae such as rheumatic fever in susceptible individuals with untreated group A streptococcal pharyngitis. In a previous study, we utilized a large panel of human peripheral blood cells to define the C-terminal protective epitope StreptInCor (medical identity), which does not induce autoimmune reactions. We recently confirmed the results in HLA-transgenic mice. In the present study, we extended the experimental assays to outbred animals (Swiss mice). Herein, we demonstrate high titers of StreptInCor-specific antibodies, as well as appropriate T-cell immune responses. No cross-reaction to cardiac myosin was detected. Additionally, immunized Swiss mice exhibited 87% survival one month after challenge with S. pyogenes. In conclusion, the data presented herein reinforce previous results in humans and animals and further emphasize that StreptInCor could be an effective and safe vaccine for the prevention of S. pyogenes infections.
Insights
A novel vaccine candidate, StreptInCor, shows promise in preventing Streptococcus pyogenes infections. Studies in mice demonstrate its safety and efficacy, inducing protective immune responses without autoimmune side effects.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Streptococcus pyogenes (S. pyogenes) causes various diseases, especially in children.
- The M protein of S. pyogenes is a key virulence factor, with N-terminal regions potentially causing autoimmune issues like rheumatic fever.
- Previous research identified the C-terminal epitope StreptInCor as a non-autoimmune protective antigen in humans and HLA-transgenic mice.
Purpose of the Study:
- To evaluate the efficacy and safety of the StreptInCor epitope in a broader animal model (outbred Swiss mice).
- To assess StreptInCor's ability to elicit specific antibody and T-cell responses.
- To confirm the absence of autoimmune cross-reactivity with cardiac myosin.
Main Methods:
- Immunization of Swiss mice with the StreptInCor epitope.
- Measurement of StreptInCor-specific antibody titers and T-cell responses.
- Assessment of cross-reactivity with cardiac myosin.
- Challenge of immunized mice with S. pyogenes to determine survival rates.
Main Results:
- High titers of StreptInCor-specific antibodies and robust T-cell immune responses were observed.
- No cross-reactivity with cardiac myosin was detected, indicating safety.
- Immunized mice showed 87% survival after S. pyogenes challenge, demonstrating significant protection.
Conclusions:
- The findings in Swiss mice corroborate previous human and animal studies.
- StreptInCor demonstrates potential as an effective and safe vaccine candidate for preventing S. pyogenes infections.
- Further development of StreptInCor as a vaccine is warranted based on demonstrated efficacy and safety profiles.
