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Published on: April 5, 2019
Immune Cross-Opsonization Within emm Clusters Following Group A Streptococcus Skin Infection: Broadening the Scope of
Hannah R Frost1,2, Delphine Laho1,3, Martina L Sanderson-Smith4
1Group A Streptococcus Research Group, Murdoch Childrens Research Institute, Melbourne, Australia.
Background:
Group A Streptococcus (GAS) skin infections are particularly prevalent in developing nations. The GAS M protein, by which strains are differentiated into >220 different emm types, is immunogenic and elicits protective antibodies. A major obstacle for vaccine development has been the traditional understanding that immunity following infection is restricted to a single emm type. However, recent evidence has led to the hypothesis of immune cross-reactivity between emm types.
Methods:
We investigated the human serological response to GAS impetigo in Fijian schoolchildren, focusing on 3 major emm clusters (E4, E6, and D4). Pre- and postinfection sera were assayed by enzyme-linked immunosorbent assay with N-terminal M peptides and bactericidal assays using the infecting-type strain, emm cluster-related strains, and nonrelated strains.
Results:
Twenty of the 53 paired sera demonstrated a ≥4-fold increase in antibody titer against the infecting type. When tested against all cluster-related M peptides, we found that 9 of 17 (53%) paired sera had a ≥4-fold increase in antibody titer to cluster-related strains as well. When grouped by cluster, the mean change to cluster-related emm types in E4 and E6 was >4-fold (5.9-fold and 19.5-fold, respectively) but for D4 was 3.8-fold. The 17 paired sera were tested in bactericidal assays against selected cluster-related and nonrelated strains. While the responses were highly variable, numerous instances of cross-reactive killing were observed.
Conclusions:
These data demonstrate that M type-specific and cross-reactive immune responses occur following skin infection. The cross-reactive immune responses frequently align with emm clusters, raising new opportunities to design multivalent vaccines with broad coverage.
Insights
Immunity to Group A Streptococcus (GAS) skin infections can be broader than previously thought. This study shows cross-reactive immune responses to GAS M types, suggesting potential for multivalent vaccines.
Area of Science:
- Immunology
- Infectious Diseases
- Vaccinology
Background:
- Group A Streptococcus (GAS) skin infections are common globally, particularly in developing countries.
- The GAS M protein is key for strain differentiation and elicits protective antibodies, but immunity was thought to be type-specific.
- Recent findings suggest potential immune cross-reactivity between different GAS emm types.
Purpose of the Study:
- To investigate human serological responses to GAS impetigo.
- To explore cross-reactivity between different GAS emm types, focusing on specific emm clusters.
Main Methods:
- Studied Fijian schoolchildren with GAS impetigo, analyzing pre- and postinfection sera.
- Used enzyme-linked immunosorbent assays (ELISA) with M peptides and bactericidal assays.
- Tested sera against infecting strains, emm cluster-related strains, and nonrelated strains.
Main Results:
- A significant increase in antibody titers against the infecting GAS type was observed in 20 of 53 paired sera.
- Over 50% of tested sera showed increased antibody titers to emm cluster-related M peptides.
- Bactericidal assays revealed cross-reactive killing of GAS strains, particularly within emm clusters E4 and E6.
Conclusions:
- Both type-specific and cross-reactive immune responses occur after GAS skin infections.
- Cross-reactivity often aligns with emm clusters, supporting the hypothesis of broader immunity.
- Findings offer new strategies for designing multivalent GAS vaccines with wider protective coverage.
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