Immunological Characterization of Malaria Glutamic Acid-Rich Protein (GARP)
Abstract: Malaria is
the most predominant parasitic infection and continues to have a significant global
impact on the health and well-being of hundreds of millions of people annually .
Plasmodium falciparum Glutamic acid-rich protein(Pf-GARP) is a parasite-derived protein
secreted during the blood stage of malaria. From the studies with field isolates, it
appears that Pf-GARP is very ... read moreimmunogenic, and it is abundant in children from endemic
areas [2, 3]. A key tool for the control, elimination, or even possible eradication of
malaria, in addition to antimalarial drugs and vector control, is an effective
vaccine. My research focuses on the immunological characterization of Pf-GARP. These
studies include the characterization of a new monoclonal antibody for Pf-GARP, mapping
of the epitope of Pf-GARP by utilizing synthetic peptides, and initial localization of
Pf-GARP using the GM7 monoclonal antibody (mAb) by immunofluorescence microscopy.
Finally, to validate the proof of concept of its clinical significance, we developed an
Enzyme-Linked Immunosorbent Assay (ELISA) to detect antibodies against Pf-GARP in the
human malaria plasma. Our screens utilized recombinant His-Pf-GARP protein as well as
defined synthetic peptides of Pf-GARP to detect and quantify antibodies in human plasma
from malaria-endemic areas in Africa. In summary, we have characterized a new mAb,
termed GM7, that is specific for Pf-GARP protein and determined a peptide (M1P6) that is
the target of the binding of the antibody (Ab) against the Pf-GARP protein. These
findings are likely to have implications for screening malaria patients that are
seropositive for Pf-GARP, and its functional significance in the pathogenesis of
cerebral and pregnancy-associated malaria.
Thesis (M.S.)--Tufts University, 2018.
Submitted to the Dept. of Pharmacology and Drug Development.
Advisor: Athar Chishti.
Committee: Miguel Stadecker.
Keyword: Pharmacology.read less
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