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Doctoral Thesis
DOI
https://doi.org/10.11606/T.87.2015.tde-04122015-181138
Document
Author
Full name
Carolina Salcedo Rivillas
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Oliveira, Maria Leonor Sarno de (President)
Botosso, Viviane Fongaro
Brandileone, Maria Cristina de Cunto
Gonçalves, Viviane Maimoni
Ruiz, Rita de Cássia
Title in Portuguese
Desenvolvimento de vacinas proteicas contra Streptococcus pneumoniae: caracterização dos componetes adjuvantes da vacina celular pertussis e análise de novas combinações vacinais.
Keywords in Portuguese
Bordetella pertussis
Streptococcus pneumoniae
Anticorpos
PspA
Sistema complemento
Vacinas
Abstract in Portuguese
Em trabalhos anteriores o nosso grupo mostrou que a vacina celular pertussis (wP) apresenta atividade adjuvante quando combinada a proteína A da superfície de Streptococcus pneumoniae (pneumococo), PspA, A formulação PspA5-wP induz altos níveis de anticorpos e proteção em camundongos após desafio com pneumococo. Neste trabalho foram avaliados os mecanismos da ação adjuvante e os componentes de B. pertussis responsáveis por este efeito. A imunização de camundongos com PspA em combinação a mutantes de B. pertussis ou componentes desta bactéria purificados mostrou que a presença da toxina pertussis (PT) capaz é essencial para induzir altos níveis de anticorpos anti-PspA e proteção significativa contra o desafio letal com pneumococo. Este efeito não foi dependente da atividade enzimática. Anticorpos anti-PspA e as proteínas do sistema complemento foram essenciais para a proteção conferida por PspA-wP. As vacinas celulares BCG e DTP combinadas a PspA, também apresentaram atividade adjuvante, induzindo anticorpos anti-PspA e proteção contra o desafio invasivo por pneumococo.
Title in English
Development of protein vaccines against Streptococcus pneumoniae: characterization of the adjuvant components of the cellular pertussis vaccine and analyze of new vaccine combinations.
Keywords in English
Bordetella pertussis
Streptococcus pneumoniae
Antibodies
Complement system
PspA
Vaccines
Abstract in English
Previously our group showed that the pneumococcal surface protein A from Streptococcus pneumoniae (pneumococcus), PspA, when combined with cellular pertussis vaccine (wP) as adjuvant, induce high levels of antibodies and mice protection on pneumococcal challenge. In this work were used mutants and purified components derived from B. pertussis for investigate the components responsible for this adjuvant effect, through of mice immunizations in combination with the PspA5 (Clade 5 PspA) antigen. Pertussis toxin (PT) was able to inducing the higher levels of PspA5 specific antibodies and significative protection against the pneumococcal lethal challenge, independently of its enzymatic effect. Was observed that in the protection conferred by the PspA5-wP formulation thus as the anti-PspA5 antibodies, the complements proteins are essentials. Lastly, prime-boost experiments showed that the cellular vaccines BCG and DTP when combined to PspA5, induced high levels of anti-PspA5 antibodies and protection against invasive challenge with pneumococcus.
 
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Publishing Date
2015-12-07
 
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