title: Immune responses to Plasmodium vivax pre-erythrocytic stage antigens in naturally exposed Duffy-negative humans: a potential model for identification of liver-stage antigens.
abstract: Duffy antigen is the receptor used by Plasmodium vivax to invade erythrocytes. Consequently, individuals lacking Duffy antigen [Fy(-)] do not develop blood-stage infections. We hypothesized that naturally exposed Fy(-) humans may develop immune responses mainly to pre-erythrocytic stages and could be used to study acquired immunity to P. vivax and to identify liver-stage antigens. We report here that antibody and IFN-gamma responses to known sporozoite antigens were significantly induced by natural exposure in Fy(-) humans, whereas responses to blood-stage antigens were significantly induced in Fy(+) humans. IFN-gamma responses to sporozoite antigens were lower in Fy(+) than in Fy(-) humans, indicating that in Fy(+) humans blood-stage infections may have suppressed T cell responses to pre-erythrocytic stages. We evaluated the immune responses to 18 novel P. vivax homologs of P. falciparum sporozoite proteins identified from the P. vivax genome sequence. Eight proteins recalled IFN-gamma responses in P. vivax-exposed but not in unexposed individuals. Of these, 3 antigens elicited IFN-gamma responses in Fy(-) but not in Fy(+) individuals. These results suggest that differential immune responses observed in naturally exposed Fy(-) and Fy(+) individuals can be exploited to identify P. vivax stage-specific antigens.
authors.affiliation: The Institute for Genomic Research, Rockville, USA. rwang@tigr.org
authors.forename: Ruobing
authors.initials: R
authors.lastname: Wang
authors.forename: Myriam
authors.initials: M
authors.lastname: Arevalo-Herrera
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Gardner
authors.forename: Anilza
authors.initials: A
authors.lastname: Bonelo
authors.forename: Jane M
authors.initials: JM
authors.lastname: Carlton
authors.forename: Andres
authors.initials: A
authors.lastname: Gomez
authors.forename: Omaira
authors.initials: O
authors.lastname: Vera
authors.forename: Liliana
authors.initials: L
authors.lastname: Soto
authors.forename: Juana
authors.initials: J
authors.lastname: Vergara
authors.forename: Shelby L
authors.initials: SL
authors.lastname: Bidwell
authors.forename: Alexander
authors.initials: A
authors.lastname: Domingo
authors.forename: Claire M
authors.initials: CM
authors.lastname: Fraser
authors.forename: Socrates
authors.initials: S
authors.lastname: Herrera
mesh_terms: D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D003429:Cross Reactions; D004375:Duffy Blood-Group System / Q000032:analysis*; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D018503:Genome, Protozoan; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008099:Liver / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D004375:Duffy Blood-Group System; D007371:Interferon-gamma