Immune Cross-Opsonization Withinemm Clusters Following Group AStreptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity

BACKGROUND: Group AStreptococcus (GAS) skin infections are particularly prevalent in developing nations. The GAS M protein, by which strains are differentiated into >220 differentemm types, is immunogenic and elicits protective antibodies. A major obstacle for vaccine development has been the tra...

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Autores principales: Frost, Hannah R, Laho, Delphine, Sanderson-Smith, Martina L, Licciardi, Paul, Donath, Susan, Curtis, Nigel, Kado, Joseph, Dale, James B, Steer, Andrew C, Smeesters, Pierre R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263703/
https://www.ncbi.nlm.nih.gov/pubmed/29020160
http://dx.doi.org/10.1093/cid/cix599
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author Frost, Hannah R
Laho, Delphine
Sanderson-Smith, Martina L
Licciardi, Paul
Donath, Susan
Curtis, Nigel
Kado, Joseph
Dale, James B
Steer, Andrew C
Smeesters, Pierre R
author_facet Frost, Hannah R
Laho, Delphine
Sanderson-Smith, Martina L
Licciardi, Paul
Donath, Susan
Curtis, Nigel
Kado, Joseph
Dale, James B
Steer, Andrew C
Smeesters, Pierre R
author_sort Frost, Hannah R
collection PubMed
description BACKGROUND: Group AStreptococcus (GAS) skin infections are particularly prevalent in developing nations. The GAS M protein, by which strains are differentiated into >220 differentemm 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 singleemm type. However, recent evidence has led to the hypothesis of immune cross-reactivity betweenemm types. METHODS: We investigated the human serological response to GAS impetigo in Fijian schoolchildren, focusing on 3 majoremm 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-relatedemm 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 withemm clusters, raising new opportunities to design multivalent vaccines with broad coverage.
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spelling pubmed-72637032020-06-04 Immune Cross-Opsonization Withinemm Clusters Following Group AStreptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity Frost, Hannah R Laho, Delphine Sanderson-Smith, Martina L Licciardi, Paul Donath, Susan Curtis, Nigel Kado, Joseph Dale, James B Steer, Andrew C Smeesters, Pierre R Clin Infect Dis Articles and Commentaries BACKGROUND: Group AStreptococcus (GAS) skin infections are particularly prevalent in developing nations. The GAS M protein, by which strains are differentiated into >220 differentemm 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 singleemm type. However, recent evidence has led to the hypothesis of immune cross-reactivity betweenemm types. METHODS: We investigated the human serological response to GAS impetigo in Fijian schoolchildren, focusing on 3 majoremm 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-relatedemm 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 withemm clusters, raising new opportunities to design multivalent vaccines with broad coverage. Oxford University Press 2017-11-01 2017-07-19 /pmc/articles/PMC7263703/ /pubmed/29020160 http://dx.doi.org/10.1093/cid/cix599 Text en © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Articles and Commentaries
Frost, Hannah R
Laho, Delphine
Sanderson-Smith, Martina L
Licciardi, Paul
Donath, Susan
Curtis, Nigel
Kado, Joseph
Dale, James B
Steer, Andrew C
Smeesters, Pierre R
Immune Cross-Opsonization Withinemm Clusters Following Group AStreptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity
title Immune Cross-Opsonization Withinemm Clusters Following Group AStreptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity
title_full Immune Cross-Opsonization Withinemm Clusters Following Group AStreptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity
title_fullStr Immune Cross-Opsonization Withinemm Clusters Following Group AStreptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity
title_full_unstemmed Immune Cross-Opsonization Withinemm Clusters Following Group AStreptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity
title_short Immune Cross-Opsonization Withinemm Clusters Following Group AStreptococcus Skin Infection: Broadening the Scope of Type-Specific Immunity
title_sort immune cross-opsonization withinemm clusters following group astreptococcus skin infection: broadening the scope of type-specific immunity
topic Articles and Commentaries
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263703/
https://www.ncbi.nlm.nih.gov/pubmed/29020160
http://dx.doi.org/10.1093/cid/cix599
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