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dc.contributor.authorFerreira, Amanda Ribeiro
dc.contributor.authorSingh, Balwan
dc.contributor.authorCabrera-Mora, Monica
dc.contributor.authorMagri De Souza, Alana Cristina
dc.contributor.authorQueiroz Marques, Maria Teresa
dc.contributor.authorPorto, Luis Cristovao Sobrino
dc.contributor.authorSantos, Fatima
dc.contributor.authorBanic, Dalma Maria
dc.contributor.authorCalvo-Calle, J. Mauricio
dc.contributor.authorOliveira-Ferreira, Joseli
dc.contributor.authorMoreno, Alberto
dc.contributor.authorLima-Junior, Josue Da Costa
dc.date2022-08-11T08:09:41.000
dc.date.accessioned2022-08-23T16:40:25Z
dc.date.available2022-08-23T16:40:25Z
dc.date.issued2014-08-22
dc.date.submitted2015-01-23
dc.identifier.citationPLoS One. 2014 Aug 22;9(8):e105828. doi: 10.1371/journal.pone.0105828. eCollection 2014. <a href="http://dx.doi.org/10.1371/journal.pone.0105828">Link to article on publisher's site</a>
dc.identifier.issn1932-6203 (Linking)
dc.identifier.doi10.1371/journal.pone.0105828
dc.identifier.pmid25148251
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39679
dc.description.abstractThe 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=25148251&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAntibodies
dc.subjectAntibody response
dc.subjectImmune response
dc.subjectMalaria
dc.subjectPlasmodium
dc.subjectRecombinant proteins
dc.subjectT cells
dc.subjectVaccines
dc.subjectImmunity
dc.subjectImmunoprophylaxis and Therapy
dc.subjectParasitic Diseases
dc.subjectParasitology
dc.titleEvaluation 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
dc.typeJournal Article
dc.source.journaltitlePloS one
dc.source.volume9
dc.source.issue8
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3479&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2476
dc.identifier.contextkey6557370
refterms.dateFOA2022-08-23T16:40:25Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/2476
dc.contributor.departmentDepartment of Pathology
dc.source.pagese105828


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<p>This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>
Except where otherwise noted, this item's license is described as <p>This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>