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dc.contributor.authorMitran, Catherine J
dc.contributor.authorMena, Angie
dc.contributor.authorLugo, Hazel
dc.contributor.authorSalanti, Ali
dc.contributor.authorNtumngia, Francis B
dc.contributor.authorAdams, John H
dc.contributor.authorArango, Eliana M
dc.contributor.authorMaestre, Amanda
dc.contributor.authorGood, Michael F
dc.contributor.authorYanow, Stephanie K
dc.date.accessioned2020-03-26T01:21:53Z
dc.date.available2020-03-26T01:21:53Z
dc.date.issued2019
dc.identifier.issn0002-9637
dc.identifier.doi10.4269/ajtmh.abstract2019
dc.identifier.urihttp://hdl.handle.net/10072/392640
dc.description.abstractDuring Plasmodium falciparum infection in pregnancy, parasites express the PfEMP1 surface antigen VAR2 CSA that mediates sequestration of infected red blood cells (iRBCs) to the placenta. Vaccines that target the DBL domains within VAR2 CSA are currently in clinical trials and the goal is to elicit antibodies that will block sequestration by interfering with the interaction of VAR2 CSA and chondroitin sulphate A (CSA) in the placenta. We are pursuing a novel strategy to develop a vaccine against P. falciparum placental malaria that is based on cross-reactivity between PvDBP from P. vivax and cryptic epitopes within VAR2 CSA. This approach is based on our previous findings that a monoclonal antibody (mAb) raised against PvDBP cross-reacts with VAR2 CSA and blocks P. falciparum adhesion to CSA in vitro. Also, we discovered that human antibodies to VAR2 CSA can be acquired outside of pregnancy and arise from exposure to PvDBP. Here, we identified an epitope within PvDBP that is the target of the mAb and showed that a peptide of this epitope completely blocks antibody recognition of VAR2 CSA. To determine whether this same epitope is involved in cross-reactivity of human antibodies to VAR2 CSA, we affinity-purified antibodies specific to this epitope from pools of sera from Colombian men and children. These purified antibodies recognized VAR2 CSA by ELISA, and strongly blocked adhesion of P. falciparum iRBCs to CSA in vitro. Furthermore, sera from multigravid African women or from rabbits immunized with VAR2 CSA do not recognize the epitope from PvDBP, demonstrating that the epitope in VAR2 CSA is cryptic. Together, these findings identify key epitopes in PvDBP elicited by natural exposure to P. vivax and mouse immunization that cross-react with cryptic epitopes in VAR2 CSA.
dc.languageEnglish
dc.publisherAmerican Society of Tropical Medicine and Hygiene
dc.relation.ispartofconferencename68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH)
dc.relation.ispartofconferencetitleAMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
dc.relation.ispartofdatefrom2019-11-20
dc.relation.ispartofdateto2019-11-24
dc.relation.ispartoflocationNational Harbor, MD
dc.relation.ispartofpagefrom299
dc.relation.ispartofpageto299
dc.relation.ispartofvolume101
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode32
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsPublic, Environmental & Occupational Health
dc.subject.keywordsTropical Medicine
dc.titleHuman antibodies to an epitope in PVDBP block adhesion of plasmodium falciparum placental parasites via cryptic epitopes in VAR2CSA
dc.typeConference output
dc.type.descriptionE3 - Conferences (Extract Paper)
dcterms.bibliographicCitationMitran, CJ; Mena, A; Lugo, H; Salanti, A; Ntumngia, FB; Adams, JH; Arango, EM; Maestre, A; Good, MF; Yanow, SK,Human antibodies to an epitope in PVDBP block adhesion of plasmodium falciparum placental parasites via cryptic epitopes in VAR2CSA, American Journal of Tropical Medicine and Hygiene, 2019, 101, pp. 299-299
dc.date.updated2020-03-26T01:01:32Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2019 American Society of Tropical Medicine and Hygiene. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.hasfulltextFull Text
gro.griffith.authorGood, Michael F.


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