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Identifying protective Streptococcus pyogenes vaccine antigens recognized by both B and T cells in human adults and
Rasmus Mortensen1,2, Thomas Nørrelykke Nissen3, Sine Fredslund1
1Statens Serum Institut, Department of Infectious Disease Immunology, Denmark.
Insights
Developing a Group A Streptococcus (GAS) vaccine is crucial. Researchers identified three promising GAS vaccine candidates (spy0469, spy1228, spy1801) that showed significant protection in a mouse model.
Area of Science:
- Bacteriology
- Immunology
- Vaccine Development
Background:
- Group A Streptococcus (GAS) infections pose a significant public health challenge, with no existing commercial vaccines.
- Understanding anti-GAS protective immunity is limited, hindering vaccine development efforts.
Purpose of the Study:
- To identify novel vaccine candidates targeting Group A Streptococcus (GAS).
- To evaluate the immunogenicity and protective efficacy of selected GAS antigens.
Main Methods:
- In silico screening identified 21 conserved, upregulated, and surface-associated GAS antigens.
- Antigens were assessed for antibody and T cell responses in humans.
- High-density peptide arrays mapped linear epitopes.
- Protective efficacy was tested in a murine GAS infection model.
Main Results:
- Four GAS antigens demonstrated significant immunological recognition.
- Three selected antigens (spy0469, spy1228, spy1801) conferred significant protection against GAS challenge in mice.
- One antigen (spy1643) did not provide protection.
Conclusions:
- Spy0469, spy1228, and spy1801 represent promising vaccine candidates against Group A Streptococcus.
- This study provides critical insights into potential targets for a GAS vaccine.
Abstract:
No commercial vaccine exists against Group A streptococci (GAS; Streptococcus pyogenes) and only little is known about anti-GAS protective immunity. In our effort to discover new protective vaccine candidates, we selected 21 antigens based on an in silico evaluation. These were all well-conserved among different GAS strains, upregulated in host-pathogen interaction studies, and predicted to be extracellular or associated with the surface of the bacteria. The antigens were tested for both antibody recognition and T cell responses in human adults and children. The antigenicity of a selected group of antigens was further validated using a high-density peptide array technology that also identified the linear epitopes. Based on immunological recognition, four targets were selected and tested for protective capabilities in an experimental GAS infection model in mice. Shown for the first time, three of these targets (spy0469, spy1228 and spy1801) conferred significant protection whereas one (spy1643) did not.
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