JCVI: Immune Responses to Plasmodium vivax Pre-erythrocytic Stage Antigens In Naturally Exposed Duffy-negative Humans: a Potential Model for Identification of Liver-stage Antigens
 
 
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Wang, R., Arevalo-Herrera, M., Gardner, M. J., Bonelo, A., Carlton, J. M., Gomez, A., Vera, O., Soto, L., Vergara, J., Bidwell, S. L., Domingo, A., Fraser, C. M., Herrera, S.

Immune Responses to Plasmodium vivax Pre-erythrocytic Stage Antigens In Naturally Exposed Duffy-negative Humans: a Potential Model for Identification of Liver-stage Antigens

Eur J Immunol. 2005 May 02; 35(6): 1859-1868.

PubMed Citation

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.