Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA

Detalhes bibliográficos
Autor(a) principal: Yanow, Stephanie K.
Data de Publicação: 2019
Outros Autores: Mitran, Catherine J., Mena, Angie, Gnidehou, Sedami, Banman, Shanna, Arango, Eliana, Lima, Barbara Andreza Soares, Lugo, Hazel, Ganesan, Aravindhan, Salanti, Ali, Mbonye, Anthony K, Ntumngia, Francis, Barakat, Khaled, Adams, John H, Kano, Flora Satiko, Carvalho, Luzia Helena, Maestre, Amanda E, Michael F, Good, Yanow, Stephanie K
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/57548
Resumo: School of Public Health. University of Alberta. Edmonton, Alberta, Canada
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spelling Yanow, Stephanie K.Mitran, Catherine J.Mena, AngieGnidehou, SedamiBanman, ShannaArango, ElianaLima, Barbara Andreza SoaresLugo, HazelGanesan, AravindhanSalanti, AliMbonye, Anthony KNtumngia, FrancisBarakat, KhaledAdams, John HKano, Flora SatikoCarvalho, Luzia HelenaMaestre, Amanda EMichael F, GoodYanow, Stephanie K2023-03-24T12:38:06Z2023-03-24T12:38:06Z2019MITRAN, Catherine J et al. Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA. mBio, v. 10, n. 5, e02343-19, 2019. doi: 10.1128/mBio.02343-19.2150-7511https://www.arca.fiocruz.br/handle/icict/5754810.1128/mBio.02343-19engAmerican Society for MicrobiologyAntibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSAinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleSchool of Public Health. University of Alberta. Edmonton, Alberta, CanadaSchool of Public Health. University of Alberta. Edmonton, Alberta, Canada.Department of Biology. Campus Saint-Jean University of Alberta. Edmonton, Alberta, Canada.School of Public Health. University of Alberta. Edmonton, Alberta, Canada.Grupo Salud y Comunidad. Facultad de Medicina. Medellín, Antioquia, Colombia.Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil.School of Public Health. University of Alberta. Edmonton, Alberta, Canada.Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.Department of Immunology and Microbiology.Centre for Medical Parasitology. University of Copenhagen. Copenhagen, Denmark.School of Public Health. Makerere University College of Health Sciences. Kampala, Uganda.College of Public Health. University of South Florida. Tampa, Florida, USA.Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.College of Public Health. University of South Florida. Tampa, Florida, USA.Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil.Grupo Salud y Comunidad. Facultad de Medicina. Medellín, Antioquia, Colombia.Institute for Glycomics. Griffith University. Southport, Queensland, Australia/Department of Medical Microbiology and Immunology. University of Alberta. Edmonton, Alberta, Canada.School of Public Health. University of Alberta. Edmonton, Alberta, Canada Australia/Department of Medical Microbiology and Immunology. University of Alberta. Edmonton, Alberta, Canada.Many pathogens evolve extensive genetic variation in virulence proteins as a strategy to evade host immunity. This poses a significant challenge for the host to develop broadly neutralizing antibodies. In Plasmodium falciparum, we show that a mechanism to circumvent this challenge is to elicit antibodies to cryptic epitopes that are not under immune pressure. We previously discovered that antibodies to the Plasmodium vivax invasion protein, PvDBP, cross-react with P. falciparum VAR2CSA, a distantly related virulence factor that mediates placental malaria. Here, we describe the molecular mechanism underlying this cross-species immunity. We identified an epitope in subdomain 1 (SD1) within the Duffy binding-like (DBL) domain of PvDBP that gives rise to cross-reactive antibodies to VAR2CSA and show that human antibodies affinity purified against a synthetic SD1 peptide block parasite adhesion to chondroitin sulfate A (CSA) in vitro. The epitope in SD1 is subdominant and highly conserved in PvDBP, and in turn, SD1 antibodies target cryptic epitopes in P. falciparum VAR2CSA. The epitopes in VAR2CSA recognized by vivax-derived SD1 antibodies (of human and mouse origin) are distinct from those recognized by VAR2CSA immune serum. We mapped two peptides in the DBL5 epsilon domain of VAR2CSA that are recognized by SD1 antibodies. Both peptides map to regions outside the immunodominant sites, and antibodies to these peptides are not elicited following immunization with VAR2CSA or natural infection with P. falciparum in pregnancy, consistent with the cryptic nature of these target epitopes. IMPORTANCE In this work, we describe a molecular mechanism of heterologous immunity between two distant species of Plasmodium. Our results suggest a mechanism that subverts the classic parasite strategy of presenting highly polymorphic epitopes in surface antigens to evade immunity to that parasite. This alternative immune pathway can be exploited to protect pregnant women from falciparum placental malaria by designing vaccines to cryptic epitopes that elicit broadly inhibitory antibodies against variant parasite strains.PlasmodiumPlasmodium falciparumPlasmodium vivaxPvDBPVAR2CSAcross-speciescryptic epitopesepitopesfalciparumheterologous immunitymalariapregnancyvivax.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALAntibodies to Cryptic Epitopes in Distant.pdfAntibodies to Cryptic Epitopes in Distant.pdfapplication/pdf2224385https://www.arca.fiocruz.br/bitstream/icict/57548/2/Antibodies%20to%20Cryptic%20Epitopes%20in%20Distant.pdff8112e6261790a92a2afeaa1e4d65f99MD52LICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/57548/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51icict/575482023-03-24 09:38:07.243oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-24T12:38:07Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA
title Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA
spellingShingle Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA
Yanow, Stephanie K.
Plasmodium
Plasmodium falciparum
Plasmodium vivax
PvDBP
VAR2CSA
cross-species
cryptic epitopes
epitopes
falciparum
heterologous immunity
malaria
pregnancy
vivax.
title_short Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA
title_full Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA
title_fullStr Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA
title_full_unstemmed Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA
title_sort Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA
author Yanow, Stephanie K.
author_facet Yanow, Stephanie K.
Mitran, Catherine J.
Mena, Angie
Gnidehou, Sedami
Banman, Shanna
Arango, Eliana
Lima, Barbara Andreza Soares
Lugo, Hazel
Ganesan, Aravindhan
Salanti, Ali
Mbonye, Anthony K
Ntumngia, Francis
Barakat, Khaled
Adams, John H
Kano, Flora Satiko
Carvalho, Luzia Helena
Maestre, Amanda E
Michael F, Good
Yanow, Stephanie K
author_role author
author2 Mitran, Catherine J.
Mena, Angie
Gnidehou, Sedami
Banman, Shanna
Arango, Eliana
Lima, Barbara Andreza Soares
Lugo, Hazel
Ganesan, Aravindhan
Salanti, Ali
Mbonye, Anthony K
Ntumngia, Francis
Barakat, Khaled
Adams, John H
Kano, Flora Satiko
Carvalho, Luzia Helena
Maestre, Amanda E
Michael F, Good
Yanow, Stephanie K
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Yanow, Stephanie K.
Mitran, Catherine J.
Mena, Angie
Gnidehou, Sedami
Banman, Shanna
Arango, Eliana
Lima, Barbara Andreza Soares
Lugo, Hazel
Ganesan, Aravindhan
Salanti, Ali
Mbonye, Anthony K
Ntumngia, Francis
Barakat, Khaled
Adams, John H
Kano, Flora Satiko
Carvalho, Luzia Helena
Maestre, Amanda E
Michael F, Good
Yanow, Stephanie K
dc.subject.en.en_US.fl_str_mv Plasmodium
Plasmodium falciparum
Plasmodium vivax
PvDBP
VAR2CSA
cross-species
cryptic epitopes
epitopes
falciparum
heterologous immunity
malaria
pregnancy
vivax.
topic Plasmodium
Plasmodium falciparum
Plasmodium vivax
PvDBP
VAR2CSA
cross-species
cryptic epitopes
epitopes
falciparum
heterologous immunity
malaria
pregnancy
vivax.
description School of Public Health. University of Alberta. Edmonton, Alberta, Canada
publishDate 2019
dc.date.issued.fl_str_mv 2019
dc.date.accessioned.fl_str_mv 2023-03-24T12:38:06Z
dc.date.available.fl_str_mv 2023-03-24T12:38:06Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv MITRAN, Catherine J et al. Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA. mBio, v. 10, n. 5, e02343-19, 2019. doi: 10.1128/mBio.02343-19.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/57548
dc.identifier.issn.en_US.fl_str_mv 2150-7511
dc.identifier.doi.none.fl_str_mv 10.1128/mBio.02343-19
identifier_str_mv MITRAN, Catherine J et al. Antibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA. mBio, v. 10, n. 5, e02343-19, 2019. doi: 10.1128/mBio.02343-19.
2150-7511
10.1128/mBio.02343-19
url https://www.arca.fiocruz.br/handle/icict/57548
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/57548/2/Antibodies%20to%20Cryptic%20Epitopes%20in%20Distant.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
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