Generation, characterization and immunogenicity of a novel chimeric recombinant protein based on Plasmodium vivax AMA-1 and MSP1(19)

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Rocha, Mariana Vilela ; Francoso, Katia Sanches ; Lima, Luciana Chagas ; Camargo, Tarsila Mendes ; Machado, Ricardo L. D. ; Costa, Fabio T. M. ; Renia, Laurent ; Nosten, Francois ; Russell, Bruce ; Rodrigues, Mauricio M. ; Soares, Irene S.

• Document type: Journal article
• Source: Vaccine; v. 35, n. 18, p. 2463-2472, APR 25 2017.
• Web of Science Citations: 4

Abstract

Plasmodium vivax is the most widely distributed malaria species and the most prevalent species of malaria in America and Asia. Vaccine development against P. vivax is considered a priority in the global program for the eradication of malaria. Earlier studies have characterized the Apical Membrane Antigen 1 (AMA-1) ectodomain and the C-terminal region (19 kDa) of the Merozoite Surface Protein 1 (MSP-1) of P. vivax as immunodominant antigens. Based on this characterization, we designed a chimeric recombinant protein containing both merozoite immunodominant domains (PvAMA1(66)-MSP1(19)). The recombinant PvAMA166-MSP119 was successfully expressed in Pichia pastoris and used to immunize two different mouse strains (BALB/c and C57BL/6) in the presence of the Poly (I:C) as an adjuvant. Immunization with the chimeric protein induced high antibody titers against both proteins in both strains of mice as detected by ELISA. Antisera also recognized the native proteins expressed on the merozoites of mature P. vivax schizonts. Moreover, this antigen was able to induce IFN-gamma-secreting cells in C57BL/6 mice. These findings indicate that this novel yeast recombinant protein containing PvAMA1(66) and PvMSP1(19) is advantageous, because of improved antibody titers and cellular immune response. Therefore, this formulation should be further developed for pre-clinical trials in non-human primates as a potential candidate for a P. vivax vaccine. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 12/13032-5 - Generation and analysis of the immunogenicity of recombinant proteins based on the different allelic forms of the circumsporozoite antigen of Plasmodium vivax aiming at the development of a universal vaccine against malaria
• Grantee: Irene da Silva Soares
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/23278-9 - Generation of chimeric recombinant proteins for vaccine development against Plasmodium vivax
• Grantee: Mariana Vilela Rocha
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/01487-0 - Functional analyze of murine antibodies induced by immunization with a chimeric recombinant protein based on different immunodominant Plasmodium vivax antigens
• Grantee: Mariana Vilela Rocha
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation