Browsing by Author "Mkindi, Catherine Gerald"

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    Immune response to new plasmodium falciparum liver stage antigens in children naturally exposed to malaria
    (Sokoine University of Agriculture, 2009) Mkindi, Catherine Gerald
    Interferon gamma (IFN-y) responses to Human Leukocyte Antigen (HLA) class 1 restricted peptide antigens have been shown to be protective against malaria in different populations where malaria is endemic. The present study examined whether newly discovered liver stage Plasmodium falciparum (P. falciparum) protein antigens, which were matched to different HLA class 1 alleles predicted to be expressed by Tanzanians, can stimulate T cells with subsequent production of IFN-y. A crossectional study from an ongoing cohort of children between the age of 0-5 years in malaria endemic area of Morogoro municipality, Tanzania, was undertaken to test IFN-y responses to the new liver stage antigens. To examine whether the these liver stage peptides stimulated T cell proliferation and IFN-y production, an enzyme linked immunospot (ELISPOT) assay was used, and results were compared to parasitological and haematological parameters of the children investigated. HLA B15 predicted specific responses were most frequent 63.6%, (21/33) when compared to responses to peptides predicted to be restricted by other HLA class 1 alleles such as HLA B35 22% (4/18) and HLA A02 15.2% (7/49) (P<0.05) by a chi square test. Children below 6 months were found to respond to the peptide antigens less frequently (7.2%, 5/70) than children above 6 months (92.8%, 65/70) (P=0.0001). Moreover, responding children above 6 months (78.8%, 26/33) were found to be protected from malaria parasitemia within two months follow up period, P=0.0003. This study confirms the presence of adaptive cell-mediated immunity to the liver stage malaria antigens in children from Tanzania and demonstrates that alleles of the HLA-B15 can effectively present antigenic epitopes. These antigens therefore provide suitable candidates for inclusion into the pool of pre-erythrocytic antigens for malaria vaccine candidates.