Acquired immune responses to the N- and C-terminal regions of Plasmodium vivax merozoite surface protein 1 in individuals exposed to malaria

This work was supported by grants from The Pew Foundation, PADCT, CNPq, and PRONEX to M.M.R. and from FAPESP to M.M.R. and H.A.D.P. I.S.S., G.L., H.A.D.P., and M.M.R. are recipients of fellowships from CNPq or CAPES.Universidade Federal do Pará. Centro de Ciências Biológicas. Departamento de Patologia. Belém, PA, Brasil / Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.Universidade de São Paulo. Departamento de Parasitologia. São Paulo, SP, Brazil.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Universidade de São Paulo. Departamento de Parasitologia. São Paulo, SP, Brazil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.In this study, we evaluated the naturally acquired immune response to Plasmodium vivax merozoite surface protein 1 (PvMSP1) in individuals with recent clinical episodes of malaria from the state of Para´, Brazil. Ten recombinant proteins representing the first 682 amino acids (aa) of the N-terminal region and one representing the final 111 aa of the C-terminal region were expressed in Escherichia coli as glutathione S-transferase fusion proteins. Both of these regions have been suggested as candidates for development of a vaccine against Plasmodium sp. The total frequencies of individuals with antibodies and cellular immune responses to PvMSP1 were high (83.8 and 75%, respectively). The recombinant proteins representing the N- and C-terminal regions were recognized by 51.4 and 64.1% of sera, respectively. The frequency of responders to the C-terminal region increased according to the number of previous malaria episodes, reaching 83.3% after four episodes. Cellular immune response was measured by in vitro proliferation and gamma interferon production. Peripheral blood mononuclear cells of 75 and 47.2% of individuals proliferated in response to stimulation by the N- and C-terminal regions, respectively. Also, we found that one protein representing the N terminus and a second representing the C terminus of PvMSP1 stimulated 54.5% of individuals to secrete gamma interferon. We concluded that PvMSP1 is immunogenic to a large proportion of individuals exposed to malaria. Our results also suggested that the C-terminal region of PvMSP1 containing the two epidermal growth factor-like domains is particularly immunogenic to antibodies and T cells during natural infection in humans