Characterization of the Plasmodium berghei MTRAP protein as a transmission blocking antigen.

Author(s)

Xiomara Alexandra Gaitan

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2019-09-11

Examining board members

Daniel Youssef Bargieri; Roberto Rudge de Moraes Barros; Maria Anice Mureb Sallum; Irene da Silva Soares

• Advisor: Daniel Youssef Bargieri

Abstract

Malaria vaccine development is one of the major challenges in biomedical sciences. The limited knowledge about the essential antigens and their function in Plasmodium life cycle, the antigenic polymorphism and the ability of the parasite to adapt are the main difficulties in vaccine development. This means that few antigens of Plasmodium have finished clinical trials and only one reached phase III. Recently, we identified the antigen MTRAP involved in transmission of the parasite form of the mammal host to the mosquito vector. The parasite proteins expressed in sexual stages playing a role in transmission are normally less polymorphic, because they are under reduced selective pressure from the immunological response of the vertebrate host, and thus may be good antigen targets for transmission blocking vaccines. Here, we tested the potential of the P. berghei MTRAP to elicit antibodies with the ability of inhibiting gamete fertilization in vitro. We induced the production of polyclonal antibodies by immunization of BALB/c mice with a recombinant PbMTRAP expressed in E. coli. Transmission blocking activity of the anti-PbMTRAP was tested through conversion assays in vitro. Immunizations with the PbMTRAP recombinant protein induced a strong antibody response in mice and these antibodies recognized the native protein by Western Blot and IFA. Furthermore, we observed that circulating anti-MTRAP in the blood stream of immunized and challenged mice reduced, in some experiments, gamete conversion into ookinetes. Our results indicate that PbMTRAP does not represent a powerful transmission blocking antigen, although marginal inhibitions of conversion in some experiments suggest it might act synergistically with other transmission blocking antigens. (AU)

• FAPESP's process: 16/16649-4 - Expression, purification and immunological analysis of p. berghei MTRAP
• Grantee: Xiomara Alexandra Gaitán
• Support Opportunities: Scholarships in Brazil - Master