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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.

Abstract
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.
AuthorsAmanda Ribeiro Ferreira, Balwan Singh, Monica Cabrera-Mora, Alana Cristina Magri De Souza, Maria Teresa Queiroz Marques, Luis Cristovão Sobrino Porto, Fatima Santos, Dalma Maria Banic, J Mauricio Calvo-Calle, Joseli Oliveira-Ferreira, Alberto Moreno, Josué Da Costa Lima-Junior
JournalPloS one (PLoS One) Vol. 9 Issue 8 Pg. e105828 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID25148251 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Epitopes, T-Lymphocyte
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DRB1 Chains
  • Immunoglobulin G
  • Malaria Vaccines
  • Membrane Proteins
  • Protozoan Proteins
  • Recombinant Proteins
  • reticulocyte-binding protein, Plasmodium vivax
Topics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Animals
  • Brazil
  • Case-Control Studies
  • Child
  • Epitopes, T-Lymphocyte (immunology)
  • Female
  • HLA-DQ beta-Chains (genetics, immunology)
  • HLA-DRB1 Chains (genetics, immunology)
  • Humans
  • Immunoglobulin G (blood)
  • Malaria Vaccines (genetics, immunology)
  • Malaria, Vivax (genetics, immunology)
  • Male
  • Membrane Proteins (genetics, immunology)
  • Mice, Inbred BALB C
  • Middle Aged
  • Molecular Sequence Data
  • Plasmodium vivax (pathogenicity)
  • Protozoan Proteins (genetics, immunology)
  • Recombinant Proteins (genetics, immunology)
  • Young Adult

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