Molecular characterization of nucleotide pyrophosphatases/ phosphodiesterases of Schistosoma mansoni and their investigation as vaccine antigens.

Author(s)

Henrique Krambeck Rofatto

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2013-04-04

Examining board members

Luciana Cezar de Cerqueira Leite; Beatriz Simonsen Stolf Carboni; Roxane Maria Fontes Piazza; Carlos Eduardo Winter; Gerhard Wunderlich

• Advisor: Luciana Cezar de Cerqueira Leite

Abstract

In this work the family of nucleotide pyrophosphatases/phosphodiesterases (NPP) from S. mansoni was characterized in order to evaluate them as vaccine antigens. The parasite has four proteins of this family (SmNPP-5a, SmNPP-5b, SmNPP-5c and SmNPP-6), whereas two of them present higher gene expression in stages that infect humans. Only anti-SmNPP-5a anitbodies showed specificity for the native protein. We use them to characterize SmNPP-5a as a glycoprotein associated with tegument membranes from adult worms. It was also found that these antibodies were able to partially inhibit the activity of the enzyme in live parasites. Thus we evaluated SmNPP-5a as recombinant vaccine antigen together with an apyrase (SmATPDase) and alkaline phosphatase (SmAP), two other nucleotidases involved in nucleotide metabolism and present in the tegument of adult parasites. SmNTDPase and SmNPP-5 were less immunogenic than SmAP. However, we only verified the reduction of parasite burden in mice immunized with SmAP, when the animals also received a subcurative treatment with praziquantel. (AU)

• FAPESP's process: 07/07685-8 - Biochemical and molecular characterization of the Nucleotide Pyrophosphtases/Phosphodiesterases (NPPs) from Schistosoma mansoni and its potencial vaccine investigation
• Grantee: Henrique Krambeck Rofatto
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)