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

Journal Article


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.

Authors


  •   Frost, H R. (external author)
  •   Laho, D (external author)
  •   Sanderson-Smith, Martina L.
  •   Licciardi, Paul (external author)
  •   Donath, Susan (external author)
  •   Curtis, Nigel (external author)
  •   Kado, Joseph (external author)
  •   Dale, James B. (external author)
  •   Steer, Andrew C. (external author)
  •   Smeesters, Pierre R. (external author)

Publication Date


  • 2017

Citation


  • 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.

Scopus Eid


  • 2-s2.0-85032873868

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1138

Number Of Pages


  • 8

Start Page


  • 1523

End Page


  • 1531

Volume


  • 65

Issue


  • 9

Place Of Publication


  • United States

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.

Authors


  •   Frost, H R. (external author)
  •   Laho, D (external author)
  •   Sanderson-Smith, Martina L.
  •   Licciardi, Paul (external author)
  •   Donath, Susan (external author)
  •   Curtis, Nigel (external author)
  •   Kado, Joseph (external author)
  •   Dale, James B. (external author)
  •   Steer, Andrew C. (external author)
  •   Smeesters, Pierre R. (external author)

Publication Date


  • 2017

Citation


  • 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.

Scopus Eid


  • 2-s2.0-85032873868

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1138

Number Of Pages


  • 8

Start Page


  • 1523

End Page


  • 1531

Volume


  • 65

Issue


  • 9

Place Of Publication


  • United States