Construction, Expression, and Evaluation of the Naturally Acquired Humoral Immune Response against Plasmodium vivax RMC-1, a Multistage Chimeric Protein.

Autor: Matos ADS; Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil., Soares IF; Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil., Baptista BO; Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil., de Souza HADS; Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil., Chaves LB; Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil., Perce-da-Silva DS; Laboratório de Imunologia Básica e Aplicada, Centro Universitário Arthur Sá Earp Neto/Faculdade de Medicina de Petrópolis (UNIFASE/FMP), Petrópolis 25680-120, RJ, Brazil.; Laboratório de Imunologia Clínica, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil., Riccio EKP; Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil., Albrecht L; Laboratório de Pesquisa em Apicomplexa, Instituto Carlos Chagas, Curitiba 81350-010, PR, Brazil., Totino PRR; Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil., Rodrigues-da-Silva RN; Laboratório de Tecnologia Imunológica, Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil., Daniel-Ribeiro CT; Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil.; Centro de Pesquisa, Diagnóstico e Treinamento em Malária (CPD-Mal), Fiocruz e Secretaria de Vigilância em Saúde, Ministério da Saúde, Rio de Janeiro 21040-900, RJ, Brazil., Pratt-Riccio LR; Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil.; Centro de Pesquisa, Diagnóstico e Treinamento em Malária (CPD-Mal), Fiocruz e Secretaria de Vigilância em Saúde, Ministério da Saúde, Rio de Janeiro 21040-900, RJ, Brazil., Lima-Junior JDC; Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-900, RJ, Brazil.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Jul 18; Vol. 24 (14). Date of Electronic Publication: 2023 Jul 18.
DOI: 10.3390/ijms241411571
Abstrakt: The PvCelTOS, PvCyRPA, and Pvs25 proteins play important roles during the three stages of the P. vivax lifecycle. In this study, we designed and expressed a P. vivax recombinant modular chimeric protein (PvRMC-1) composed of the main antigenic regions of these vaccine candidates. After structure modelling by prediction, the chimeric protein was expressed, and the antigenicity was assessed by IgM and IgG (total and subclass) ELISA in 301 naturally exposed individuals from the Brazilian Amazon. The recombinant protein was recognized by IgG (54%) and IgM (40%) antibodies in the studied individuals, confirming the natural immunogenicity of the epitopes that composed PvRMC-1 as its maintenance in the chimeric structure. Among responders, a predominant cytophilic response mediated by IgG1 (70%) and IgG3 (69%) was observed. IgM levels were inversely correlated with age and time of residence in endemic areas ( p < 0.01). By contrast, the IgG and IgM reactivity indexes were positively correlated with each other, and both were inversely correlated with the time of the last malaria episode. Conclusions: The study demonstrates that PvRMC-1 was successfully expressed and targeted by natural antibodies, providing important insights into the construction of a multistage chimeric recombinant protein and the use of naturally acquired antibodies to validate the construction.
Databáze: MEDLINE
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