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Expression, purification and immunological evaluation of truncated forms and hybrids of Pneumococcal Surface Protein A (PspA).

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Author(s):
Michelle Darrieux Sampaio Bertoncini
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Luciana Cezar de Cerqueira Leite; Ises de Almeida Abrahamsohn; Luiza Guilherme Guglielmi; Marilis do Valle Marques; Fabiana Cristina Pimenta
Advisor: Luciana Cezar de Cerqueira Leite
Abstract

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. (AU)