Immune response to new plasmodium falciparum liver stage antigens in children naturally exposed to malaria
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Date
2009
Authors
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Publisher
Sokoine University of Agriculture
Abstract
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.
Description
Master's Theses
Keywords
Malaria, children-malaria, Human leukocyte antigens, Plasmodium falciparum liver stage antigens