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Identification of immunostimulatory antigens in Group A Streptococcus-derived vesicles
Meztlli O Gaytán1, Rebecca S Dookie1, Sayoni Chakraborty1
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm SE-171 65, Sweden.
Insights
Extracellular vesicles derived from Group A Streptococcus (GAS) show promise as a vaccine platform. Intranasal immunization in mice generated strong antibody and T cell responses, identifying key antigens for potential broad protection against GAS infections.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Group A Streptococcus (GAS) infections necessitate an effective vaccine.
- Bacterial extracellular vesicles (EVs) are emerging as promising vaccine platforms.
Purpose of the Study:
- To evaluate the immunostimulatory potential of GAS-derived EVs for intranasal immunization in mice.
- To identify immunogenic GAS antigens for vaccine development.
Main Methods:
- Intranasal administration of GAS-derived EVs in a mouse model.
- Humoral and cellular immune response analysis (IgG, IgA, T cell responses).
- Immunoprecipitation, mass spectrometry, and western blotting to identify antigens.
- ELISA to assess antigen recognition by human sera and IL-17A production.
Main Results:
- Intranasal immunization induced robust specific IgG and IgA antibody responses.
- Significant Th17 and Th1 cell-mediated immune responses were observed.
- Seven immunogenic GAS proteins (MtsA, BMP, PrsA1, PrsA2, MetQ, MalX, GlnP) were identified.
- These antigens are recognized by human sera and stimulate IL-17A production, showing high conservation across GAS strains.
Conclusions:
- GAS-derived EVs are effective intranasal vaccine platforms inducing humoral and cellular immunity.
- Identified GAS antigens hold potential as broadly protective vaccine candidates against diverse GAS M-types.
- Further research into these antigens could lead to a novel GAS vaccine.
Abstract:
An effective vaccine against Streptococcus pyogenes (Group A Streptococcus, GAS) is urgently needed. Bacteria-derived extracellular vesicles (EVs) are emerging as promising vaccine platforms. In this study, we evaluated the immunostimulatory properties of GAS-derived EVs when administered intranasally in mice. Immunization induced a strong humoral response, including pathogen-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies. Additionally, we observed local and systemic T cell responses, specifically a robust Th17 response along with a modest but statistically significant Th1 response. Through immunoprecipitation coupled with mass spectrometry and western blotting, we identified seven immunogenic proteins, including the lipoproteins MtsA, BMP, PrsA1, PrsA2, MetQ, MalX, and the glutamine transporter GlnP. These antigens were recognized by human sera from both healthy individuals and patients with necrotizing soft tissue infection. Finally, we demonstrate that these antigens stimulate production and secretion of IL-17A by lung cells and splenocytes and that they are highly conserved across diverse GAS M-types, highlighting their potential as broadly protective vaccine candidates.
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