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Genetic diversity and immunogenicity analysis of MAEBL and RON2 of Plasmodium vivax

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Author(s):
Najara Carneiro Bittencourt
Total Authors: 1
Document type: Master's Dissertation
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
Defense date:
Examining board members:
Fabio Trindade Maranhão Costa; Jörg Kobarg; Gerhard Wunderlich
Advisor: Letusa Albrecht; Fabio Trindade Maranhão Costa
Abstract

Last year, 212 million malaria cases were estimated worldwide. Plasmodium vivax accounts for 41% of the cases of the disease outside the African continent. Unlike Plasmodium falciparum, infections caused by P. vivax are rarely lethal. However, P. vivax has a significant impact on the productivity of local populations. The emergence of drug-resistant strains and complications on P. vivax infection make it extremely necessary to intensify research on definitive control methods such as the development of vaccines. Several proteins have been studied aiming to find a good vaccine candidate. MAEBL is a chimeric molecule expressed on infected erythrocytes that presents two domains involved in the erythrocyte invasion process (M1 and M2). M2 domain is the most important one for merozoite invasion, and it exhibits higher adhesiveness. Recently, it has been shown that MAEBL is also expressed in the salivary sporozoite gland and infected hepatocytes. Moreover, the gene that codifies MAEBL was identified in different Plasmodium species, including P. vivax. RON2 is a conserved protein that belongs to Apicomplexa phylum. It is expressed in late schizonts, secreted by organelles called roptries in the merozoite and it is also involved in the erythrocyte invasion process. In this process AMA-1 together with RON proteins establish the moving junction structure, which makes a connection between the merozoite and the erythrocyte. The characteristics of MAEBL and RON2 open perspectives for the development of an experimental vaccine. It is important to characterize the pattern of genetic diversity of these proteins, as well as to evaluate the immunogenicity of them in order to find a good vaccine candidate. For it to be possible, PCR and sequence analysis were performed. The MAEBL and RON2 proteins were expressed and tested by ELISA to evaluate their immunogenicity against the plasma of infected individuals. A low genetic diversity was evidenced for both genes. Pvron2 did not present non-synonymous mutations and Pvmaebl presented 7 non-synonymous mutations. The reactivity indices of naturally acquired IgM and IgG antibodies against MAEBL were 4.54% for IgM and 55.6% for total IgG. IgG antibodies naturally acquired against RON2 were present in 8.33% of the individuals analyzed. Therefore, MAEBL and RON2 proteins are conserved and immunogenic, thus reaffirming them as potential vaccine candidates (AU)

FAPESP's process: 15/02808-0 - Genetic diversity and immunogenicity of MAEBL amongst Plasmodium vivax field isolates
Grantee:Najara Carneiro Bittencourt
Support Opportunities: Scholarships in Brazil - Master