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https://www.arca.fiocruz.br/handle/icict/10938
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ArtigoDireito Autoral
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- IOC - Artigos de Periódicos [12642]
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EVALUATION OF NATURALLY ACQUIRED IGG ANTIBODIES TO A CHIMERIC AND NON-CHIMERIC RECOMBINANT SPECIES OF PLASMODIUM VIVAX RETICULOCYTE BINDING PROTEIN-1: LACK OF ASSOCIATION WITH HLA-DRB1*/DQB1* IN MALARIA EXPOSED INDIVIDUALS FROM THE BRAZILIAN AMAZON
Autor(es)
Afiliação
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Atlanta, Geogia, USA.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Atlanta, Georgia, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Laboratório de Criopreservação e Histocompatibilidade. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Laboratório de Criopreservação e Histocompatibilidade. Rio de Janeiro, RJ, Brasil.
Fundação Nacional de Saúde. Departamento de Entomologia. Laboratório Central. Porto Velho, RO, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Referência Nacional de Simulídeos e Oncocercose. Rio de Janeiro, RJ, Brasil.
University of Massachusetts. Medical School. Department of Pathology. Worcester, Massachusetts, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Department of Medicine. Division of Infectious Diseases. Atlanta, Geogia, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Atlanta, Geogia, USA.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Atlanta, Georgia, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Laboratório de Criopreservação e Histocompatibilidade. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Laboratório de Criopreservação e Histocompatibilidade. Rio de Janeiro, RJ, Brasil.
Fundação Nacional de Saúde. Departamento de Entomologia. Laboratório Central. Porto Velho, RO, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Referência Nacional de Simulídeos e Oncocercose. Rio de Janeiro, RJ, Brasil.
University of Massachusetts. Medical School. Department of Pathology. Worcester, Massachusetts, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Department of Medicine. Division of Infectious Diseases. Atlanta, Geogia, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
Resumo em Inglês
The development of modular constructs that include antigenic regions targeted by protective immune responses is an
attractive approach for subunit vaccine development. However, a main concern of using these vaccine platforms is how to
preserve the antigenic identity of conformational B cell epitopes. In the present study we evaluated naturally acquired
antibody responses to a chimeric protein engineered to contain a previously defined immunodominant domain of the
Plasmodium vivax reticulocyte binding protein-1 located between amino acid positions K435-I777. The construct also includes
three regions of the cognate protein (F571-D587, I1745-S1786 and L2235-E2263) predicted to contain MHC class II promiscuous T
cell epitopes. Plasma samples from 253 naturally exposed individuals were tested against this chimeric protein named
PvRMC-RBP1 and a control protein that includes the native sequence PvRBP123-751 in comparative experiments to study the
frequency of total IgG and IgG subclass reactivity. HLA-DRB1 and HLA-DQB1 allelic groups were typed by PCR-SSO to
evaluate the association between major HLA class II alleles and antibody responses. We found IgG antibodies that
recognized the chimeric PvRMC-RBP1 and the PvRBP123-751 in 47.1% and 60% of the studied population, respectively.
Moreover, the reactivity index against both proteins were comparable and associated with time of exposure (p,0.0001) and
number of previous malaria episodes (p,0.005). IgG subclass profile showed a predominance of cytophilic IgG1 over other
subclasses against both proteins tested. Collectively these studies suggest that the chimeric PvRMC-RBP1 protein retained
antigenic determinants in the PvRBP1435–777 native sequence. Although 52.9% of the population did not present detectable
titers of antibodies to PvRMC-RBP1, genetic restriction to this chimeric protein does not seem to occur, since no association
was observed between the HLA-DRB1* or HLA-DQB1* alleles and the antibody responses. This experimental evidence
strongly suggests that the identity of the conformational B cell epitopes is preserved in the chimeric protein.
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