About this item:

468 Views | 480 Downloads

Author Notes:

Email: alberto.moreno@emory.edu (AM); josue@ioc.fiocruz.br (JCLJ)

See publication for full list of author contributions.

We are grateful to all individuals who participated in this study, for their cooperation and generous donation of blood, which made this study possible.

We thank the Secretary of Health of Rondonia State and the Laboratorio Central – LACEN of Rondonia for supporting fieldwork and Stacey Lapp for critical reading of the manuscript.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

This research was supported by the Brazilian National Research Council - CNPq, Fiocruz, US National Institutes of Health, NIAID grant R01-AI064766, R21AI094402-01 and R21AI095718-01 and the Yerkes National Primate Research Center Base Grant No RR00165 awarded by the National Center for Research Resources of the National Institutes of Health.

JMCC's involvement was supported by NIH-U19-57319.

ARF was the recipient of a CNPq Fellowship.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • MEROZOITE SURFACE PROTEIN-1
  • CELLULAR IMMUNE-RESPONSES
  • GLUTAMATE-RICH PROTEIN
  • GROWTH IN-VITRO
  • CIRCUMSPOROZOITE PROTEIN
  • PROTECTIVE IMMUNITY
  • VACCINE CANDIDATE
  • NAIVE VOLUNTEERS
  • CLINICAL MALARIA
  • FALCIPARUM
  • Malaria
  • Antibodies
  • Plasmodium
  • Recombinant proteins
  • Antibody response
  • T cells
  • Immune response
  • Vaccines

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

Show all authors Show less authors

Tools:

Journal Title:

PLoS ONE

Volume:

Volume 9, Number 8

Publisher:

, Pages e105828-e105828

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

Copyright 2014 Ferreira et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote