The Specificity of Naturally Acquired Antibodies that Bind to the Surface of VAR2CSA-Expressing P. Falciparum Infected Erythrocytes

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dc.contributor.authorNgati, Elise Penvadga
dc.date.accessioned2017-12-18T21:32:27Z
dc.date.available2017-12-18T21:32:27Z
dc.date.issued2015-12
dc.descriptionM.S. University of Hawaii at Manoa 2015.
dc.descriptionIncludes bibliographical references.
dc.description.abstractPlacental malaria (PM) caused by Plasmodium falciparium is a major health problem affecting both the mother and fetus. Previous studies showed that high anti-VAR2CSA IgG levels improve pregnancy outcome, e.g., increase birth weight, reduce anemia, lower placental parasitemia, and prevent drug treatment failures. VAR2CSA has 6 DBL domains. Pregnant women produce antibodies (Ab) that bind to the surface of CSA binding IE. It is not clear if these Ab bind to one or multiple DBL domains. The goal of this study was to determine the specificity of naturally acquired Ab that bind to CS2 IE. In our study, clinical information and archival plasma samples collected between 1996 -2001 at delivery from 1,377 pregnant Cameroonian women living in Yaoundé (low transmission) were used. Since the samples were collected prior to implementation of intermittent preventive treatment and insecticide-treated bed nets, natural immunity determined the presence or absence of PM. Plasma from women who were PM- and PM+ of different gravidities were screened for Ab to full length VAR2CSA (FV2) and other DBL domains using a bead-based multiplex assay. The results identified which DBL domains each woman recognized. Then, a subset of samples was tested for Ab binding to the surface of CS2 IE (express VAR2CSA) and to 3D7 IE (non CSA-binding phenotypes). IE were incubated with plasma, then anti-human IgG FITC, and the amount of fluorescence per cell surface area was determined by FACS. In this study using 100 samples with different levels of Ab to FV2, a Significant correlation between Ab to FV2 and cell surface staining intensity was obtained (r = 0.62; P< .0001: Spearman Correlation) and levels of reactivity to the different DBL domains recognized by each woman was reported. Most domains showed a modest correlation of Ab levels and CSS. DBL1( Corr=0.42, P<.0001), DBL1+2(Corr=0.49, P<.0001), DBL2(Corr=0.23, P=0.025), ID1 D2a(Corr=0.37, P=0.0002), DBL3(Corr=0.48, P<.0001), DBL4(Corr=0.45, P<.0001 ), DBL5(Corr=0.45, P<.0001 ), and DBL6 (Corr=0.49, P<.0001 )
dc.identifier.urihttp://hdl.handle.net/10125/51174
dc.language.isoeng
dc.publisher[Honolulu] : [University of Hawaii at Manoa], [December 2015]
dc.relationTheses for the degree of Master of Science (University of Hawaii at Manoa). Tropical Medicine & Med Micro
dc.titleThe Specificity of Naturally Acquired Antibodies that Bind to the Surface of VAR2CSA-Expressing P. Falciparum Infected Erythrocytes
dc.typeThesis
dc.type.dcmiText

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