title: Association of interferon-gamma responses to pre-erythrocytic stage vaccine candidate antigens of Plasmodium falciparum in young Kenyan children with improved hemoglobin levels: XV. Asembo Bay Cohort Project.
abstract: Previous studies in animal models have revealed an association between interferon-gamma (IFN-gamma), produced by CD8+ T cells and irradiated sporozoite-induced sterile immunity. To determine whether IFN-gamma can serve as a marker of pre-erythrocytic protective immunity in individuals naturally exposed to malaria, we characterized IFN-gamma and lymphocyte proliferative responses to previously defined CD8+ cytotoxic T lymphocyte (CTL) epitopes from six pre-erythrocytic stage antigens in 107 children six months to two years old from a community-based birth cohort in western Kenya. We found that IFN-gamma positive responders had higher hemoglobin (Hb) levels and significantly reduced prevalence of severe malarial anemia one month after the test compared with IFN-gamma non-responders, suggesting that IFN-gamma immune responses to these pre-erythrocytic antigens were associated with protection against malarial anemia. Children who responded by lymphocyte proliferation had a significantly longer time to first documented malaria parasitemia after birth; however, there was no correlation between the presence of lymphocyte proliferative response and higher Hb levels. We propose that IFN-gamma production could be used as a potential marker of protective immunity against malaria associated anemia in young children living in malaria holoendemic areas.
authors.affiliation: Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: John M O
authors.initials: JM
authors.lastname: Ong'echa
authors.forename: Altaf A
authors.initials: AA
authors.lastname: Lal
authors.forename: Dianne J
authors.initials: DJ
authors.lastname: Terlouw
authors.forename: Feiko O
authors.initials: FO
authors.lastname: Ter Kuile
authors.forename: Simon K
authors.initials: SK
authors.lastname: Kariuki
authors.forename: Venkatchalam
authors.initials: V
authors.lastname: Udhayakumar
authors.forename: Alloys S S
authors.initials: AS
authors.lastname: Orago
authors.forename: Allen W
authors.initials: AW
authors.lastname: Hightower
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Nahlen
authors.forename: Ya Ping
authors.initials: YP
authors.lastname: Shi
mesh_terms: D000740:Anemia / Q000097:blood / Q000209:etiology; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000150:complications / Q000276:immunology* / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D006454:Hemoglobins; D016052:Protozoan Vaccines; D007371:Interferon-gamma