Protective immunogenicity of group a streptococcal M-related proteins

James 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 Courtney

Research output: Contribution to journalArticle

8 Citations (Scopus)

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

Fingerprint

Streptococcus
Proteins
Vaccines
Virulence
Immune Sera
Assays
streptococcal M protein
Rabbits
Antibodies
Immunosorbents
Pediatrics
Sequence Analysis
Epitopes
Membrane Proteins
Enzyme-Linked Immunosorbent Assay
Genes
Antigens
Peptides
Infection
Serum

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

Dale, J., Niedermeyer, S. E., Agbaosi, T., Hysmith, N. D., Penfound, T. A., Hohn, C. M., ... Courtney, H. (2015). Protective immunogenicity of group a streptococcal M-related proteins. Clinical and Vaccine Immunology, 22(3), 344-350. https://doi.org/10.1128/CVI.00795-14

Protective immunogenicity of group a streptococcal M-related proteins. / Dale, James; Niedermeyer, Shannon E.; Agbaosi, Tina; Hysmith, Nicholas D.; Penfound, Thomas A.; Hohn, Claudia M.; Pullen, Matthew; Bright, Michael I.; Murrell, Daniel S.; Shenep, Lori E.; Courtney, Harry.

In: Clinical and Vaccine Immunology, Vol. 22, No. 3, 01.03.2015, p. 344-350.

Research output: Contribution to journalArticle

Dale, J, Niedermeyer, SE, Agbaosi, T, Hysmith, ND, Penfound, TA, Hohn, CM, Pullen, M, Bright, MI, Murrell, DS, Shenep, LE & Courtney, H 2015, 'Protective immunogenicity of group a streptococcal M-related proteins', Clinical and Vaccine Immunology, vol. 22, no. 3, pp. 344-350. https://doi.org/10.1128/CVI.00795-14
Dale J, Niedermeyer SE, Agbaosi T, Hysmith ND, Penfound TA, Hohn CM et al. Protective immunogenicity of group a streptococcal M-related proteins. Clinical and Vaccine Immunology. 2015 Mar 1;22(3):344-350. https://doi.org/10.1128/CVI.00795-14
Dale, James ; Niedermeyer, Shannon E. ; Agbaosi, Tina ; Hysmith, Nicholas D. ; Penfound, Thomas A. ; Hohn, Claudia M. ; Pullen, Matthew ; Bright, Michael I. ; Murrell, Daniel S. ; Shenep, Lori E. ; Courtney, Harry. / Protective immunogenicity of group a streptococcal M-related proteins. In: Clinical and Vaccine Immunology. 2015 ; Vol. 22, No. 3. pp. 344-350.
@article{9fc03ed7c21640a289cebe5bee47d61f,
title = "Protective immunogenicity of group a streptococcal M-related proteins",
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.",
author = "James Dale and Niedermeyer, {Shannon E.} and Tina Agbaosi and Hysmith, {Nicholas D.} and Penfound, {Thomas A.} and Hohn, {Claudia M.} and Matthew Pullen and Bright, {Michael I.} and Murrell, {Daniel S.} and Shenep, {Lori E.} and Harry Courtney",
year = "2015",
month = "3",
day = "1",
doi = "10.1128/CVI.00795-14",
language = "English (US)",
volume = "22",
pages = "344--350",
journal = "Clinical and Vaccine Immunology",
issn = "1556-6811",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - Protective immunogenicity of group a streptococcal M-related proteins

AU - Dale, James

AU - Niedermeyer, Shannon E.

AU - Agbaosi, Tina

AU - Hysmith, Nicholas D.

AU - Penfound, Thomas A.

AU - Hohn, Claudia M.

AU - Pullen, Matthew

AU - Bright, Michael I.

AU - Murrell, Daniel S.

AU - Shenep, Lori E.

AU - Courtney, Harry

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84923923273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923923273&partnerID=8YFLogxK

U2 - 10.1128/CVI.00795-14

DO - 10.1128/CVI.00795-14

M3 - Article

VL - 22

SP - 344

EP - 350

JO - Clinical and Vaccine Immunology

JF - Clinical and Vaccine Immunology

SN - 1556-6811

IS - 3

ER -