title: Immune characterization of Plasmodium falciparum parasites with a shared genetic signature in a region of decreasing transmission.
abstract: As the intensity of malaria transmission has declined, Plasmodium falciparum parasite populations have displayed decreased clonal diversity resulting from the emergence of many parasites with common genetic signatures (CGS). We have monitored such CGS parasite clusters from 2006 to 2013 in Thiès, Senegal, using the molecular barcode. The first, and one of the largest observed clusters of CGS parasites, was present in 24% of clinical isolates in 2008, declined to 3.4% of clinical isolates in 2009, and then disappeared. To begin to explore the relationship between the immune responses of the population and the emergence and decline of specific parasite genotypes, we have determined whether antibodies to CGS parasites correlate with their prevalence. We measured (i) antibodies capable of inhibiting parasite growth in culture and (ii) antibodies recognizing the surfaces of infected erythrocytes (RBCs). IgG obtained from volunteers in 2009 showed increased reactivity to the surfaces of CGS-parasitized erythrocytes over IgG from 2008. Since P. falciparum EMP-1 (PfEMP-1) is a major variant surface antigen, we used var Ups quantitative reverse transcription-PCR (qRT-PCR) and sequencing with degenerate DBL1α domain primers to characterize the var genes expressed by CGS parasites after short-term in vitro culture. CGS parasites show upregulation of UpsA var genes and 2-cysteine-containing PfEMP-1 molecules and express the same dominant var transcript. Our work indicates that the CGS parasites in this cluster express similar var genes, more than would be expected by chance in the population, and that there is year-to-year variation in immune recognition of surface antigens on CGS parasite-infected erythrocytes. This study lays the groundwork for detailed investigations of the mechanisms driving the expansion or contraction of specific parasite clones in the population.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA Laboratory of Bacteriology and Virology, Le Dantec Hospital, Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Bei
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ababacar
authors.initials: A
authors.lastname: Diouf
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Center for Communicable Disease Dynamics, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Larremore
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Ulf
authors.initials: U
authors.lastname: Ribacke
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Tullo
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Eli L
authors.initials: EL
authors.lastname: Moss
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Neafsey
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Daniels
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Amir E
authors.initials: AE
authors.lastname: Zeituni
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Iguosadolo
authors.initials: I
authors.lastname: Nosamiefan
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA Simmons College, Boston, Massachusetts, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Volkman
authors.affiliation: Laboratory of Bacteriology and Virology, Le Dantec Hospital, Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Ambroise D
authors.initials: AD
authors.lastname: Ahouidi
authors.affiliation: Laboratory of Parasitology and Mycology, Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Daouda
authors.initials: D
authors.lastname: Ndiaye
authors.affiliation: Laboratory of Bacteriology and Virology, Le Dantec Hospital, Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Tandakha
authors.initials: T
authors.lastname: Dieye
authors.affiliation: Laboratory of Bacteriology and Virology, Le Dantec Hospital, Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Souleymane
authors.initials: S
authors.lastname: Mboup
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Center for Communicable Disease Dynamics, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Caroline O
authors.initials: CO
authors.lastname: Buckee
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA dfwirth@hsph.harvard.edu.
authors.forename: Dyann F
authors.initials: DF
authors.lastname: Wirth
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D016000:Cluster Analysis; D058893:DNA Barcoding, Taxonomic; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000635:transmission; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D012675:Senegal / Q000453:epidemiology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum