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Published on: December 19, 2020
Opsonic Activity of Conservative Versus Variable Regions of the Group A Streptococcus M Protein
Chuankai Dai1, Zeinab G Khalil2, Waleed M Hussein1,3
1School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
Abstract:
Group A Streptococcus (GAS) and GAS-associated infections are a global challenge, with no licensed GAS vaccine on the market. The GAS M protein is a critical virulence factor in the fight against GAS infection, and it has been a primary target for GAS vaccine development. Measuring functional opsonic antibodies against GAS is an important component in the clinical development path for effective vaccines. In this study, we compared the opsonic activity of two synthetic, self-adjuvanting subunit vaccines containing either the J8- or 88/30-epitope in Swiss outbred mice using intranasal administration. Following primary immunization and three boosts, sera were assessed for IgG activity using ELISA, and opsonization activity against seven randomly selected clinical isolates of GAS was measured. Vaccine constructs containing the conservative J8-epitope showed significant opsonic activity against six out of the seven GAS clinical isolates, while the vaccine containing the variable 88/30-epitope did not show any significant opsonic activity.
Insights
A new study found that a vaccine targeting the J8-epitope of Group A Streptococcus (GAS) induced significant opsonic antibody activity against most GAS strains. This offers a promising avenue for developing effective GAS vaccines.
Area of Science:
- Bacteriology
- Vaccinology
- Immunology
Background:
- Group A Streptococcus (GAS) infections pose a global health challenge with no available vaccine.
- The GAS M protein is a key virulence factor and a primary target for vaccine development.
- Assessing functional opsonic antibodies is crucial for evaluating vaccine efficacy.
Purpose of the Study:
- To compare the opsonic activity of two synthetic subunit vaccines (J8-epitope vs. 88/30-epitope) against Group A Streptococcus.
- To evaluate the potential of these vaccine candidates in a mouse model.
Main Methods:
- Two synthetic, self-adjuvanting subunit vaccines (J8-epitope and 88/30-epitope) were administered intranasally to Swiss outbred mice.
- Mice received a primary immunization followed by three boosts.
- Serum IgG activity was measured by ELISA, and opsonization activity against seven clinical GAS isolates was assessed.
Main Results:
- The vaccine containing the conserved J8-epitope demonstrated significant opsonic activity against six of the seven tested GAS clinical isolates.
- The vaccine based on the variable 88/30-epitope showed no significant opsonic activity.
- ELISA confirmed IgG activity in sera post-vaccination.
Conclusions:
- The J8-epitope subunit vaccine shows promise for inducing functional antibodies against a majority of GAS strains.
- Targeting conserved epitopes like J8 may be a more effective strategy for developing a broadly protective GAS vaccine.
- Further research is warranted to advance this vaccine candidate for clinical development.
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