Immune responses to Plasmodium vivax pre-erythrocytic stage antigens in naturally exposed Duffy-negative humans: a potential model for identification of liver-stage antigens.
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.
Wang
Ruobing
R
The Institute for Genomic Research, Rockville, USA. rwang@tigr.org
Arevalo-Herrera
Myriam
M
Gardner
Malcolm J
MJ
Bonelo
Anilza
A
Carlton
Jane M
JM
Gomez
Andres
A
Vera
Omaira
O
Soto
Liliana
L
Vergara
Juana
J
Bidwell
Shelby L
SL
Domingo
Alexander
A
Fraser
Claire M
CM
Herrera
Socrates
S
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*
D000953:Antigens, Protozoan; D004375:Duffy Blood-Group System; D007371:Interferon-gamma