Protective immunogenicity of group a streptococcal M-related proteins

James B. Dale, Shannon E. Niedermeyer, Tina Agbaosi, Nicholas D. Hysmith, Thomas A. Penfound, Claudia M. Hohn, Matthew Pullen, Michael I. Bright, Daniel S. Murrell, Lori E. Shenep, Harry S. Courtney

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Many previous studies have focused on the surface M proteins of group A streptococci (GAS) as virulence determinants and protective antigens. However, the majority of GAS isolates express M-related protein (Mrp) in addition to M protein, and both have been shown to be required for optimal virulence. In the current study, we evaluated the protective immunogenicity of Mrp to determine its potential as a vaccine component that may broaden the coverage of M protein-based vaccines. Sequence analyses of 33 mrp genes indicated that there are three families of structurally related Mrps (MrpI, MrpII, and MrpIII). N-terminal peptides of Mrps were cloned, expressed, and purified from M type 2 (M2) (MrpI), M4 (MrpII), and M49 (MrpIII) GAS. Rabbit antisera against the Mrps reacted at high titers with the homologous Mrp, as determined by enzyme-linked immunosorbent assay, and promoted bactericidal activity against GAS emm types expressing Mrps within the same family. Mice passively immunized with rabbit antisera against MrpII were protected against challenge infections with M28 GAS. Assays for Mrp antibodies in serum samples from 281 pediatric subjects aged 2 to 16 indicated that the Mrp immune response correlated with increasing age of the subjects. Affinity-purified human Mrp antibodies promoted bactericidal activity against a number of GAS representing different emm types that expressed an Mrp within the same family but showed no activity against emm types expressing an Mrp from a different family. Our results indicate that Mrps have semiconserved N-terminal sequences that contain bactericidal epitopes which are immunogenic in humans. These findings may have direct implications for the development of GAS vaccines.

Original languageEnglish (US)
Pages (from-to)344-350
Number of pages7
JournalClinical and Vaccine Immunology
Volume22
Issue number3
DOIs
StatePublished - Mar 1 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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