ASSOCIATION OF INTERFERON-γ RESPONSES TO PRE-ERYTHROCYTIC STAGE VACCINE CANDIDATE ANTIGENS OF PLASMODIUM FALCIPARUM IN YOUNG KENYAN CHILDREN WITH IMPROVED HEMOGLOBIN LEVELS: XV. ASEMBO BAY COHORT PROJECT

JOHN M. O. ONG’ECHA Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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ALTAF A. LAL Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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DIANNE J. TERLOUW Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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FEIKO O. TER KUILE Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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SIMON K. KARIUKI Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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VENKATCHALAM UDHAYAKUMAR Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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ALLOYS S. S. ORAGO Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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ALLEN W. HIGHTOWER Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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BERNARD L. NAHLEN Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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YA PING SHI Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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Previous studies in animal models have revealed an association between interferon-γ (IFN- γ), produced by CD8+ T cells and irradiated sporozoite-induced sterile immunity. To determine whether IFN-γ can serve as a marker of pre-erythrocytic protective immunity in individuals naturally exposed to malaria, we characterized IFN-γ 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- γ positive responders had higher hemoglobin (Hb) levels and significantly reduced prevalence of severe malarial anemia one month after the test compared with IFN- γ non-responders, suggesting that IFN- γ 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- γ production could be used as a potential marker of protective immunity against malaria associated anemia in young children living in malaria holoendemic areas.

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