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Doctoral Thesis
DOI
10.11606/T.87.2007.tde-18042008-090617
Document
Author
Full name
Michelle Darrieux Sampaio Bertoncini
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Leite, Luciana Cezar de Cerqueira (President)
Abrahamsohn, Ises de Almeida
Guglielmi, Luiza Guilherme
Marques, Marilis do Valle
Pimenta, Fabiana Cristina
Title in Portuguese
Expressão, purificação e avaliação imunológica de formas truncadas e hibrídos da proteína de superfície de pneumococo A (PspA).
Keywords in Portuguese
Complemento.
Proteínas recombinantes
Streptococcus pneumoniae
Vacinas
Abstract in Portuguese
Streptococcus pneumoniae é um importante agente causador de pneumonia, meningite e septicemia. O alto custo e a cobertura limitada da vacina conjugada atual reforçam a necessidade de se desenvolver uma vacina mais abrangente e acessível. A proteína de superfície de pneumococo A (PspA) é imunogênica e protetora em modelos animais; porém, devido à sua diversidade - há 6 clados e 3 famílias de PspA - uma vacina baseada em PspA deverá incluir fragmentos das duas famílias prevalentes (1 e 2). Neste estudo, foram produzidos fragmentos contendo a região N-terminal de PspA das famílias 1 e 2, e proteínas híbridas - contendo fusões destes fragmentos. Os anticorpos gerados contra os híbridos reconheceram PspAs nativas das duas famílias, foram capazes de se ligar a bactérias íntegras, e de aumentar a deposição de complemento em sua superfície. Finalmente, a imunização de camundongos com os híbridos foi capaz de proteger contra desafio com pneumococos contendo PspAs diversas, mostrando que estes seriam candidatos promissores na composição de uma vacina anti-pneumocócica.
Title in English
Expression, purification and immunological evaluation of truncated forms and hybrids of Pneumococcal Surface Protein A (PspA).
Keywords in English
Complement.
Recombinant proteins
Streptococcus pneumoniae
Vaccines
Abstract in English
Streptococcus pneumoniae is an important cause of pneumonia, meningitis and septicaemia. The high cost and limited coverage of the available conjugate vaccine reinforce the need for cost effective strategies, with broader coverage. Pneumococcal Surface Protein A (PspA) is immunogenic and protective in animal models; however, due to its diversity - there are six clades and threee families of PspA - a PspA based vaccine should include fragments of each major family (1 and 2). In the present study, we have produced fragments of the N-terminal region of PspAs families 1 and 2, and hybrid proteins - containing fusions of these fragments. Sera made against the hybrids induced antibodies that recognized PspAs from both families; these sera were also able to bind pneumococcal strains bearing diverse PspAs, and to increase complement deposition on their surface. Finally, immunization of mice with PspA hybrids was protective against challenge with pneumococci bearing diverse PspAs, showing that these hybrids should constitute promising candidates in an anti-pneumococcal vaccine.
 
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Tese.pdf (2.77 Mbytes)
Publishing Date
2008-09-22
 
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