Immune Cross-Opsonization Within emm Clusters Following Group A Streptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity

Authors

Hannah R. Frost, Murdoch Children's Research Institute, Universite Libre De Bruxelles
Delphine Laho, Universite Libre De Bruxelles, Murdoch Children's Research Institute
Martina L. Sanderson-Smith, University of WollongongFollow
Paul Licciardi, Murdoch Children's Research Institute, University of Melbourne
Susan Donath, University of Melbourne
Nigel Curtis, University of Melbourne
Joseph Kado, Fiji National University, Fiji Rheumatic Heart Disease Control Program, Colonial War Memorial Hospital
James B. Dale, Veterans Affairs Medical Center, USA, University of Tennessee
Andrew C. Steer, Murdoch Children's Research Institute, University of Melbourne, Royal Children's Hospital Melbourne
Pierre R. Smeesters, University of Melbourne, Murdoch Children's Research Institute, Universite Libre De BruxellesFollow

RIS ID

117008

Publication Details

Frost, H. R., Laho, D., Sanderson-Smith, M. L., Licciardi, P., Donath, S., Curtis, N., Kado, J., Dale, J. B., Steer, A. C. & Smeesters, P. R. (2017). Immune Cross-Opsonization Within emm Clusters Following Group A Streptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity. Clinical Infectious Diseases, 65 (9), 1523-1531.

Abstract

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.