Analysis of the role of genes bir in the host-pathogen relation and development of proteoliposomes for the use in vaccines against blood stage forms of Plasmodium.

Author(s)

Wesley Luzetti Fotoran

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2017-03-28

Examining board members

Gerhard Wunderlich; Letusa Albrecht; Daniel Youssef Bargieri; Pietro Ciancaglini; Claudio Romero Farias Marinho

• Advisor: Gerhard Wunderlich

Abstract

The relation between mammals and Plasmodium comprise infections with adaptive reflections for both sides. The immune evasion by parasites and immune acquisition by the host against important antigens are end points of a long process. Variant genes and proteins of the parasite can exert a role in this process by enbling immune evasion, cytoadherence resulting in the maintainence of the infective process. We tested three experimental approaches focusing on the following points:1-Show if variant BIR antigens are associated with cytoadherence during murine infections 2- The role of a transgene under the control of a variant gene promoter in adaptation to infection in hosts which express or not the transgene 3- Creation of a vaccine model applicable to any relevant antigen in infections with Plasmodium. As results we showed that: 1-BIR antigenes are likely not related to cito adhesion in the murine model. Cytoadherence in this model is probably related to exported parasite proteins with LCCL domains 2-bir promoters can be modulated during infection in hosts which which differ in one unique gene.The effects observed in this case was an increase in parasitemia, anergy and immune tolerance without affecting the morbidity of infection in the host. These effects are apparently mediated by parasite subpopulations producing exosomes that signal from the parasite to the host.3- We generated a system for recombinant protein production where antigens are fused to GPI and then integrated onto liposomes for vaccine usage. The proof of principle was the use of recombinant PfRH5-GPI as vaccine which elicited antibodies with strong blocking activity in P. falciparum cultures. Together we have shown that the host environment is capable of modulating the activity of variant bir gene promoters and that proteoliposomes loaded with relevant malarial antigens such as PfRH5, are potentially protective when used as malaria vaccine. (AU)

• FAPESP's process: 12/18617-1 - Role of variant antigens in the immunity against murine Plasmodium: Estimating the influence of variant proteins BIR in cytoadherence and their potential as vaccine using novel means of administration.
• Grantee: Wesley Luzetti Fotoran
• Support Opportunities: Scholarships in Brazil - Doctorate