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
Department of Pathology
Immunity | Immunoprophylaxis and Therapy | Parasitic Diseases | Parasitology
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.
Antibodies, Antibody response, Immune response, Malaria, Plasmodium, Recombinant proteins, T cells, Vaccines
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DOI of Published Version
PLoS One. 2014 Aug 22;9(8):e105828. doi: 10.1371/journal.pone.0105828. eCollection 2014. Link to article on publisher's site
Ferreira, Amanda Ribeiro; Singh, Balwan; Cabrera-Mora, Monica; Magri De Souza, Alana Cristina; Queiroz Marques, Maria Teresa; Porto, Luis Cristovao Sobrino; Santos, Fatima; Banic, Dalma Maria; Calvo-Calle, J. Mauricio; Oliveira-Ferreira, Joseli; Moreno, Alberto; and Lima-Junior, Josue Da Costa, "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" (2014). Open Access Articles. 2476.
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