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

dc.creatorYanow, Stephanie K.
dc.creatorMitran, Catherine J.
dc.creatorMena, Angie
dc.creatorGnidehou, Sedami
dc.creatorBanman, Shanna
dc.creatorArango, Eliana
dc.creatorLima, Barbara Andreza Soares
dc.creatorLugo, Hazel
dc.creatorGanesan, Aravindhan
dc.creatorSalanti, Ali
dc.creatorMbonye, Anthony K
dc.creatorNtumngia, Francis
dc.creatorBarakat, Khaled
dc.creatorAdams, John H
dc.creatorKano, Flora Satiko
dc.creatorCarvalho, Luzia Helena
dc.creatorMaestre, Amanda E
dc.creatorMichael F, Good
dc.creatorYanow, Stephanie K
dc.date2023-03-24T12:38:06Z
dc.date2023-03-24T12:38:06Z
dc.date2019
dc.date.accessioned2023-09-26T20:55:18Z
dc.date.available2023-09-26T20:55:18Z
dc.identifierMITRAN, 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.identifier2150-7511
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/57548
dc.identifier10.1128/mBio.02343-19
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8866193
dc.descriptionMany 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.rightsopen access
dc.subjectPlasmodium
dc.subjectPlasmodium falciparum
dc.subjectPlasmodium vivax
dc.subjectPvDBP
dc.subjectVAR2CSA
dc.subjectcross-species
dc.subjectcryptic epitopes
dc.subjectepitopes
dc.subjectfalciparum
dc.subjectheterologous immunity
dc.subjectmalaria
dc.subjectpregnancy
dc.subjectvivax.
dc.titleAntibodies to Cryptic Epitopes in Distant Homologues Underpin a Mechanism of Heterologous Immunity between Plasmodium vivax PvDBP and Plasmodium falciparum VAR2CSA
dc.typeArticle


Este ítem pertenece a la siguiente institución