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dc.contributor.authorAndrew R. Williamsen_US
dc.contributor.authorAlexander D. Douglasen_US
dc.contributor.authorKazutoyo Miuraen_US
dc.contributor.authorJoseph J. Illingworthen_US
dc.contributor.authorPrateek Choudharyen_US
dc.contributor.authorLinda M. Murungien_US
dc.contributor.authorJulie M. Furzeen_US
dc.contributor.authorAbabacar Dioufen_US
dc.contributor.authorOlivo Miottoen_US
dc.contributor.authorCécile Crosnieren_US
dc.contributor.authorGavin J. Wrighten_US
dc.contributor.authorDominic P. Kwiatkowskien_US
dc.contributor.authorRick M. Fairhursten_US
dc.contributor.authorCarole A. Longen_US
dc.contributor.authorSimon J. Draperen_US
dc.contributor.otherUniversity of Oxforden_US
dc.contributor.otherNational Institute of Allergy and Infectious Diseasesen_US
dc.contributor.otherCentre for Geographic Medicine Researchen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherWellcome Trust Sanger Instituteen_US
dc.contributor.otherWellcome Trust Centre for Human Geneticsen_US
dc.identifier.citationPLoS Pathogens. Vol.8, No.11 (2012)en_US
dc.description.abstractNo vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause the symptoms and severe manifestations of malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced antibodies. Here we show that antibodies against PfRH5 efficiently inhibit the in vitro growth of short-term-adapted parasite isolates from Cambodia, and that the EC 50 values of antigen-specific antibodies against PfRH5 are lower than those against PfAMA1. Since antibody responses elicited by multiple antigens are speculated to improve the efficacy of blood-stage vaccines, we conducted detailed assessments of parasite growth inhibition by antibodies against PfRH5 in combination with antibodies against seven other merozoite antigens. We found that antibodies against PfRH5 act synergistically with antibodies against certain other merozoite antigens, most notably with antibodies against other erythrocyte-binding antigens such as PfRH4, to inhibit the growth of a homologous P. falciparum clone. A combination of antibodies against PfRH4 and basigin, the erythrocyte receptor for PfRH5, also potently inhibited parasite growth. This methodology provides the first quantitative evidence that polyclonal vaccine-induced antibodies can act synergistically against P. falciparum antigens and should help to guide the rational development of future multi-antigen vaccines.en_US
dc.rightsMahidol Universityen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectImmunology and Microbiologyen_US
dc.titleEnhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigensen_US
Appears in Collections:Scopus 2011-2015

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