1. Immune Cross-Opsonization Within emm Clusters Following Group A Streptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity.
- Author
-
Frost, Hannah R., Laho, Delphine, Sanderson-Smith, Martina L., Licciardi, Paul, Donath, Susan, Curtis, Nigel, Kado, Joseph, Dale, James B., Steer, Andrew C., and Smeesters, Pierre R.
- Subjects
ANTIGEN-antibody reactions ,COMMUNICABLE diseases ,ENZYME-linked immunosorbent assay ,PEPTIDES ,SERODIAGNOSIS ,SKIN diseases ,STREPTOCOCCAL diseases ,VACCINES - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF