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STABILITY OF INTERFERON- AND INTERLEUKIN-10 RESPONSES TO PLASMODIUM FALCIPARUM LIVER STAGE ANTIGEN-1 AND THROMBOSPONDIN-RELATED ADHESIVE PROTEIN IN RESIDENTS OF A MALARIA HOLOENDEMIC AREA

The stability of anti-malarial immunity will influence the interpretation of immunologic endpoints during malaria vaccine trials conducted in endemic areas. Therefore, we evaluated cytokine responses to Plasmodium falciparum liver stage antigen-1 (LSA-1) and thrombospondin-related adhesive protein (TRAP) by Kenyans from a holoendemic area at a 9-month interval. The proportion of adults with interferon- (IFN-) responses to 9-mer LSA-1 peptides was similar at both time-points, whereas responses from children decreased (P < 0.05). Response to the longer, 23-mer LSA-1 peptide was variable, decreasing in adults and children over time (P < 0.02 and P < 0.001, respectively). The proportion of children with IFN- responses to either antigen at the second time-point was significantly lower than that of adults, yet more adults responded to 9-mer TRAP peptides (P < 0.02). In contrast, the proportion of interleukin-10 responses to LSA-1 and TRAP was similar at both time-points for both age groups. Most noteworthy was that even when the repeat cross-sectional frequency of cytokine responses was the same, these responses were not generated by the same individuals. This suggests that cytokine responses to LSA-1 and TRAP are transient under natural exposure conditions.

Received September 8, 2005. Accepted for publication December 8, 2005.

Acknowledgments: The authors thank Dan Rosen at the Centers from Disease Control and Prevention, Kisumu, Kenya, for statistical assistance and Marilyn McHugh at Case Western Reserve University and Kiprotich Chelimo at the Kenya Medical Research Institute, Kisumu, for laboratory assistance.

Financial support: This research was funded by NIH Grant U01 AI 43906 and published with permission of the Director of the Kenya Medical Research Institute.

^* Address correspondence to Ann M. Moormann, Center for Global Health and Diseases, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Wolstein Research Building 4-130, Cleveland, OH 44106-7286. E-mail: moorms{at}case.edu

Authors’ addresses: Ann M. Moormann, Center for Global Health and Diseases, Case Western Reserve University, 2103 Cornell Road, 4-130 Wolstein Research Building, Cleveland, OH 44106-7286, E-mail: moorms{at}case.edu. Chandy C. John, Division of Pediatric Infectious Diseases, University of Minnesota Medical School, 420 Delaware Street, SE, Minneapolis, MN 55455, E-mail: ccj{at}umn.edu. Peter Odada Sumba, Center for Vector Biology and Control Research, Kenya Medical Research Institute, PO Box 1578, Kisumu, Kenaya, E-mail: POdada{at}kisian.mimcom.net. Daniel J. Tisch, Department of Epidemiology and Biostatistics School of Medicine, WG-37, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4945, E-mail: daniel.tisch{at}case.edu. Paula Embury, Center for Global Health and Diseases, Case Western Reserve University, 2103 Cornell Road, 4th Floor, Wolstein Research Building, Cleveland, OH 44106-7286, E-mail: pbe{at}case.edu. James W. Kazura, Center for Global Health and Diseases, Case Western Reserve University, 2103 Cornell Road, 4th Floor, Wolstein Research Building, Cleveland, OH 44106-7286, E-mail: jxk14{at}case.edu.

Reprint requests: Ann M. Moormann, Center for Global Health and Diseases, Case Western Reserve University, 2103 Cornell Road, 4-130 Wolstein Research Building, Cleveland, OH 44106-7286.