Towards a Vaccine Against Rheumatic Fever

Rheumatic fever (RF) is an autoimmune disease which affects more than 20 million children in developing countries. It is triggered by Streptococcus pyogenes throat infection in untreated susceptible individuals. Carditis, the most serious manifestation of the disease, leads to severe and permanent v...

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Main Authors: L. Guilherme, K. C. Faé, F. Higa, L. Chaves, S. E. Oshiro, S. Freschi de Barros, C. Puschel, M. A. Juliano, A. C. Tanaka, G. Spina, J. Kalil
Format: Article
Language:English
Published: Wiley 2006-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1080/17402520600877026
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author L. Guilherme
K. C. Faé
F. Higa
L. Chaves
S. E. Oshiro
S. Freschi de Barros
C. Puschel
M. A. Juliano
A. C. Tanaka
G. Spina
J. Kalil
author_facet L. Guilherme
K. C. Faé
F. Higa
L. Chaves
S. E. Oshiro
S. Freschi de Barros
C. Puschel
M. A. Juliano
A. C. Tanaka
G. Spina
J. Kalil
author_sort L. Guilherme
collection DOAJ
description Rheumatic fever (RF) is an autoimmune disease which affects more than 20 million children in developing countries. It is triggered by Streptococcus pyogenes throat infection in untreated susceptible individuals. Carditis, the most serious manifestation of the disease, leads to severe and permanent valvular lesions, causing chronic rheumatic heart disease (RHD). We have been studying the mechanisms leading to pathological autoimmunity in RF/RHD for the last 15 years. Our studies allowed us a better understanding of the cellular and molecular pathogenesis of RHD, paving the way for the development of a safe vaccine for a post-infection autoimmune disease. We have focused on the search for protective T and B cell epitopes by testing 620 human blood samples against overlapping peptides spanning 99 residues of the C-terminal portion of the M protein, differing by one amino acid residue. We identified T and B cell epitopes with 22 and 25 amino acid residues, respectively. Although these epitopes were from different regions of the C-terminal portion of the M protein, they showed an identical core of 16 amino acid residues. Antibodies against the B cell epitope inhibited bacterial invasion/adhesion in vitro. Our results strongly indicated that the selected T and B cell epitopes could potentially be protective against S. pyogenes.
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spelling doaj-art-95a5f30988da4781ae794a09db1a3a452025-02-03T01:09:38ZengWileyClinical and Developmental Immunology1740-25221740-25302006-01-01132-412513210.1080/17402520600877026Towards a Vaccine Against Rheumatic FeverL. Guilherme0K. C. Faé1F. Higa2L. Chaves3S. E. Oshiro4S. Freschi de Barros5C. Puschel6M. A. Juliano7A. C. Tanaka8G. Spina9J. Kalil10School of Medicine, Heart Institute (InCor), University of São Paulo, São Paulo, BrazilSchool of Medicine, Heart Institute (InCor), University of São Paulo, São Paulo, BrazilSchool of Medicine, Heart Institute (InCor), University of São Paulo, São Paulo, BrazilSchool of Medicine, Heart Institute (InCor), University of São Paulo, São Paulo, BrazilSchool of Medicine, Heart Institute (InCor), University of São Paulo, São Paulo, BrazilSchool of Medicine, Heart Institute (InCor), University of São Paulo, São Paulo, BrazilSchool of Medicine, Heart Institute (InCor), University of São Paulo, São Paulo, BrazilFederal University of São Paulo (UNIFESP), São Paulo, BrazilSchool of Medicine, Heart Institute (InCor), University of São Paulo, São Paulo, BrazilSchool of Medicine, Heart Institute (InCor), University of São Paulo, São Paulo, BrazilSchool of Medicine, Heart Institute (InCor), University of São Paulo, São Paulo, BrazilRheumatic fever (RF) is an autoimmune disease which affects more than 20 million children in developing countries. It is triggered by Streptococcus pyogenes throat infection in untreated susceptible individuals. Carditis, the most serious manifestation of the disease, leads to severe and permanent valvular lesions, causing chronic rheumatic heart disease (RHD). We have been studying the mechanisms leading to pathological autoimmunity in RF/RHD for the last 15 years. Our studies allowed us a better understanding of the cellular and molecular pathogenesis of RHD, paving the way for the development of a safe vaccine for a post-infection autoimmune disease. We have focused on the search for protective T and B cell epitopes by testing 620 human blood samples against overlapping peptides spanning 99 residues of the C-terminal portion of the M protein, differing by one amino acid residue. We identified T and B cell epitopes with 22 and 25 amino acid residues, respectively. Although these epitopes were from different regions of the C-terminal portion of the M protein, they showed an identical core of 16 amino acid residues. Antibodies against the B cell epitope inhibited bacterial invasion/adhesion in vitro. Our results strongly indicated that the selected T and B cell epitopes could potentially be protective against S. pyogenes.http://dx.doi.org/10.1080/17402520600877026
spellingShingle L. Guilherme
K. C. Faé
F. Higa
L. Chaves
S. E. Oshiro
S. Freschi de Barros
C. Puschel
M. A. Juliano
A. C. Tanaka
G. Spina
J. Kalil
Towards a Vaccine Against Rheumatic Fever
Clinical and Developmental Immunology
title Towards a Vaccine Against Rheumatic Fever
title_full Towards a Vaccine Against Rheumatic Fever
title_fullStr Towards a Vaccine Against Rheumatic Fever
title_full_unstemmed Towards a Vaccine Against Rheumatic Fever
title_short Towards a Vaccine Against Rheumatic Fever
title_sort towards a vaccine against rheumatic fever
url http://dx.doi.org/10.1080/17402520600877026
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