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

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.

Allele Specificity of Gamma Interferon Responses to the Carboxyl-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 1 by Kenyan Adults with Naturally Acquired Immunity to Malaria

“…Preimmunization IFN-␥ responses in malaria-experienced populations are important for establishing baseline values for subsequent vaccine trials, although as we have shown in this study that such responses vary greatly within and between individuals. Similar to our previous cross-sectional studies of pre-erythrocytic-stage malaria peptides (31,32), while an individual's responses varied between time points, the overall proportions of responders to each allele were similar across each season. Given the large proportion of adults responding to the 3D7 allele in this study, outcome measurements for an MSP1 vaccine tested in areas in which the disease is endemic may have to incorporate a fold increase over baseline and prolonged duration of immune response in order to distinguish between a vaccine-attributable affect and normal variation as the result of natural exposure.…”

Changes in Antigen-Specific Cytokine and Chemokine Responses to Plasmodium falciparum Antigens in a Highland Area of Kenya after a Prolonged Absence of Malaria Exposure

“…In the present study, antigen-specific IFN-␥ levels decreased in the absence of transmission, but antigen-specific IL-10 levels also decreased in the absence of transmission. These findings are similar to those of a study we conducted in a different highland area of Kenya (4) but differ from studies we conducted in an area of malaria holoendemicity in Kenya (52) and in the same highland area as in the present study at two time points of much higher malaria incidence (53). In those studies, IL-10 levels did not differ significantly over time.…”

Interferon-γresponses toPlasmodium falciparumvaccine candidate antigens decrease in the absence of malaria transmission

“…Indeed, the findings of some studies suggest that the breadth and magnitude of IFN- γ responses reduce quickly upon resolution of infection (John et al, 2004; Riley et al, 1993) leading to the suggestion that IFN- γ responses may be a marker of recent exposure. In contrast, repeat-cross-sectional studies in highland Kenya showed that IFN- γ responses to pre-erythrocytic antigens LSA-1 (John et al, 2000) and TRAP were stable over periods of very low malaria transmission (Moormann et al, 2009), possibly showing that IFN- γ responses may not be a good indicator of past exposure. Interestingly, a recent study suggested that IFN- γ responses to blood stage antigens are a marker of recent exposure but not protection, while IFN- γ responses to pre-erythrocytic antigen driven are associated with protection (Jagannathan et al, 2015).…”