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-γ 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-γ 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-γ responses in P. vivax-exposed but not in unexposed individuals. Of these, 3 antigens elicited IFN-γ 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.