학술논문
StreptInCor: a model of anti-Streptococcus pyogenes vaccine reviewed.
Document Type
Academic Journal
Author
Guilherme L; Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil ; Institute for Immunology Investigation, National Institute of Science and Technology, University of São Paulo, São Paulo, Brazil ; Laboratório de Imunologia, Instituto do Coração (HC-FMUSP), Av. Dr. Eneas de Carvalho Aguiar, 44, São Paulo, SP 05403-903 Brazil.; Postol E; Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil ; Institute for Immunology Investigation, National Institute of Science and Technology, University of São Paulo, São Paulo, Brazil.; Ferreira FM; Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil ; Institute for Immunology Investigation, National Institute of Science and Technology, University of São Paulo, São Paulo, Brazil.; DeMarchi LM; Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil.; Kalil J; Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil ; Institute for Immunology Investigation, National Institute of Science and Technology, University of São Paulo, São Paulo, Brazil ; Clinical Immunology and Allergy Division, School of Medicine, University of São Paulo, São Paulo, Brazil.
Source
Publisher: BioMed Central Country of Publication: England NLM ID: 101532391 Publication Model: eCollection Cited Medium: Print ISSN: 2038-0305 (Print) Linking ISSN: 20380305 NLM ISO Abbreviation: Auto Immun Highlights Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2038-0305
Abstract
Streptococcus pyogenes infections remain a health problem in multiple countries because of poststreptococcal sequelae, such as rheumatic fever and rheumatic heart disease. The epidemiological growth of streptococcal diseases in undeveloped and developing countries has encouraged many groups to study vaccine candidates for preventing group A streptococcus infections. We developed a vaccine epitope (StreptInCor) composed of 55 amino acid residues of the C-terminal portion of the M protein that encompasses both T and B cell protective epitopes. Using human blood samples, we showed that the StreptInCor epitope is recognized by individuals bearing different HLA class II molecules and could be considered a universal vaccine epitope. In addition, the StreptInCor molecular structure was solved by nuclear magnetic resonance spectroscopy, and a series of structural stability experiments was performed to elucidate its folding/unfolding mechanism. Using BALB-c and HLA class II transgenic mice, we evaluated the immune response over an extended period and found that StreptInCor was able to induce a robust immune response in both models. No cross-reaction was observed against cardiac proteins. The safety of the vaccine epitope was evaluated by analyzing histopathology, and no autoimmune or pathological reactions were observed in the heart or other organs. Vaccinated BALB/c mice challenged with a virulent strain of S. pyogenes had 100 % survival over 30 days. Taking all results into account, StreptInCor could be a safe and effective vaccine against streptococcus-induced disease.