NIH Research Festival
Malaria is a life-threatening disease that affects a quarter of a billion people each year through the bite of female Anopheles mosquitoes. Currently there are two approved anti-infection vaccines, both contain essentially the carboxyl-terminal half of the Plasmodium falciparum circumsporozoite protein (CSP). In addition, a human monoclonal antibody (mAb) that binds an epitope in the amino-terminal region, not currently in either vaccine, has been shown to passively protect in human clinical trials. Given the partial efficacy of the anti-infection vaccines, we are further investigating the biology, subcellular localization, and structure of the CSP. We previously observed that native CSP, a disordered protein, may undergo structural changes on the surface of infectious sporozoites. Furthermore, efforts to crystallize a near full-length recombinant PfCSP protein, identified as PfCSPM3, using different enriched fractions yielded crystals that unfortunately did not diffract. To pursue a different approach, we have developed a recombinant CSP specific murine mAb with a human Rhinovirus 3C proteolytic site for planned electron microscopy studies. We will initially study PfCSPM3 and subsequently, if possible, native CSP from enriched preparations of whole or fractionated sporozoites. The results from these ongoing efforts will be presented. An improved understanding of native CSP may further support the evaluation of a full-length recombinant CSP malaria vaccine.
Scientific Focus Area: Structural Biology
This page was last updated on Monday, September 25, 2023