Protective immunogenicity of group A streptococcal M-related proteins.

Autor:	Dale JB; Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Microbiology, Immunology and Biochemistry, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA jbdale@uthsc.edu., Niedermeyer SE; Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA., Agbaosi T; Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA., Hysmith ND; Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Penfound TA; Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA., Hohn CM; Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA., Pullen M; Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA., Bright MI; Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA., Murrell DS; Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA., Shenep LE; Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA., Courtney HS; Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA.
Jazyk:	angličtina
Zdroj:	Clinical and vaccine immunology : CVI [Clin Vaccine Immunol] 2015 Mar; Vol. 22 (3), pp. 344-50. Date of Electronic Publication: 2015 Jan 28.
DOI:	10.1128/CVI.00795-14
Abstrakt:	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. (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
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