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Doctoral Thesis
DOI
10.11606/T.87.2013.tde-06112013-102932
Document
Author
Full name
Adriana Tonet Moreno
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Miyaji, Eliane Namie (President)
Almeida, Maria Elisabete Sbrogio de
Fukasawa, Lucila Okuyama
Gonçalves, Viviane Maimoni
Martins, Elizabeth Angelica Leme
Title in Portuguese
Avaliação da variabilidade do candidato vacinal PspC (Pneumococcal surface protein C) em isolados de Streptococcus pneumoniae do Hospital Universitário da Universidade de São Paulo.
Keywords in Portuguese
Streptococcus
Immunoblotting
Infecções respiratórias
Vacinas
Virulência
Abstract in Portuguese
Streptococcus pneumoniae é o agente causador de diversas doenças, tais como meningite e pneumonia. PspC (Pneumococcal surface protein C) foi descrito como um importante candidato vacinal proteico de ampla cobertura e com baixo custo de produção. Trata-se de um fator de virulência, capaz de ligar-se ao Fator H (FH) e a IgA secretório (sIgA). Como PspC é um antígeno polimórfico, é crucial a avaliação da sua variabilidade. Foi determinado o grupo de PspC de treze linhagens de pneumococo isoladas no Hospital Universitário da Universidade de São Paulo. Soros contra diferentes grupos de PspC foram produzidos e PspC do grupo 3 (PspC3) foi capaz de induzir anticorpos que reconhecem diferentes grupos de PspC. Foi observada ainda uma pequena redução na ligação de FH e sIgA por anticorpos anti-PspC3 em ensaios in vitro. No entanto, não foi possível observar proteção contra um modelo de colonização da nasofaringe de camundongos através da imunização com PspC3, possivelmente por deficiências no modelo experimental.
Title in English
Evaluation of the variability of the vaccine candidate PspC (Pneumococcal surface protein C) in Streptococcus pneumoniae isolates from the University Hospital of the University of São Paulo.
Keywords in English
Streptococcus
Immunoblotting
Respiratory infections
Vaccines
Virulence
Abstract in English
Streptococcus pneumoniae is the causative agent of several diseases, such as meningitis and pneumonia. PspC (Pneumococcal surface protein C) has been described as an important vaccine candidate protein as it could provide wide coverage with low cost of production. PspC is a virulence factor capable of binding to Factor H (FH) and secretory IgA (sIgA). PspC is polymorphic antigen, and therefore it is crucial to evaluate its variability. In the present work we have determined the PspC group of 13 pneumococcal isolates obtained at the University Hospital of the University of São Paulo. Antisera against different PspC groups were produced and PspC group 3 (PspC3) was able to induce antibodies that recognized different groups of PspC. Antibodies to PspC3 reduced binding of FH and sIgA to pneumococcus in in vitro assays. However, no protection was observed against a murine model of nasopharyngeal colonization by immunization with PspC3. This was possibly due to deficiencies in the experimental model.
 
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Publishing Date
2014-01-16
 
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