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. 2009 Sep;81(3):489-95.

Stability of interferon-gamma and interleukin-10 responses to Plasmodium falciparum liver stage antigen 1 and thrombospondin-related adhesive protein immunodominant epitopes in a highland population from Western Kenya

Ann M Moormann  1 , Peter Odada Sumba, Daniel J Tisch, Paula Embury, Charles H King, James W Kazura, Chandy C John
Affiliations

Stability of interferon-gamma and interleukin-10 responses to Plasmodium falciparum liver stage antigen 1 and thrombospondin-related adhesive protein immunodominant epitopes in a highland population from Western Kenya

Ann M Moormann et al. Am J Trop Med Hyg. 2009 Sep.

Abstract

Long-term planning to prevent malaria epidemics requires in-depth understanding of immunity to Plasmodium falciparum in areas of unstable transmission. Cytokine responses to immunodominant epitope peptides from liver stage antigen 1 (LSA-1) and thrombospondin-related adhesive protein (TRAP) were evaluated over a nine-month interval in adults and children in Kenya from a malaria epidemic-prone highland area after several years of low transmission. The proportion and magnitude of interferon-gamma ELISPOT responses and the proportion of interleukin-10 responders to LSA-1 and TRAP peptides tended to be higher in adults than children. Frequencies of interferon-gamma responders to these peptides were similar at the two time points, but responses were not consistently generated by the same persons. These results suggest that T cell memory to pre-erythrocytic stage malaria antigens is maintained but may be unavailable for consistent detection in peripheral blood, and that these antigens induce both pro-inflammatory and anti-inflammatory cytokine responses in this population.

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Figures

Figure 1
Figure 1
Cases of clinical malaria in the highland site of Kipsamoite, Kenya, 1996–2002 All persons diagnosed with malaria at the local health center in Kipsamoite during 1996–2002 are reported by month. Clinical malaria was defined either by documented fever accompanied by positive blood smear for Plasmodium falciparum parasites or by clinical diagnosis (in the absence of microscopy confirmation). Black arrows indicate when the immunologic measurements were conducted in November 2000 (time point 1) and August 2001 (time point 2) on a subset of residents enrolled in this study.
Figure 2
Figure 2
Magnitude of interferon-gamma (IFN-γ) ELISPOT responses to liver stage antigen 1 (LSA-1) and thrombospondin-related adhesive protein (TRAP) peptides for adults and children. Box plot distribution of the number of IFN-γ spot-forming units (SFU) per million peripheral blood mononuclear cells (PBMC) minus the phosphate-buffered saline (PBS) background (range = 0–5 SFU per well) for each peptide tested in adults and children with positive responses at either time point (because there was no significant difference in magnitude of response between time points, results were combined). Adults had significantly higher median IFN-γ levels compared with children for ls94 ( P = 0.013), tr51 ( P = 0.021), tr539 ( P = 0.026), and tp6 ( P = 0.038). The magnitude of IFN-γ ELISPOT responses did not significantly differ for ls84, ls1881 or T3 when comparing children with adults. Circles represent outliers above the 95th percentile and asterisks are extreme points ≥ 99th percentile.
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