Collaborative Projects 

Dr. Joe Smith (Seattle BioMed) and Dr. Chetan Chitnis (ICGEB)
This project will test the hypothesis that antibody responses focused on the PvDBPII-DARC interaction site will be more effective at blocking parasite invasion.  To focus the antibody response on critical DARC binding residues, we will introduce N-glycosylation sites to “mask” different surfaces of PvDBPII immunogens.  As a specific test of our hypothesis, we will introduce multiple N-glycosylation sites into either the putative DARC interaction site or on the opposite surface where the polymorphism resides. Prior to immunization, we will compare the function and antigenicity of modified PvDBPII proteins produced in Pichia pastoris.  Function will be assessed using a flow cytometry based erythrocyte binding assay or binding to recombinant DARC-Fc protein.  Antigenicity will be assessed as ability to reverse binding inhibitory activity of anti-PvDBPII sera.   The best performing antigens (i.e. bind DARC-Fc and inhibit sera activity) will be tested as vaccine immunogens.  Modified immunogens will be compared to wild-type for eliciting antibodies that block rPvDBPII binding to reticulocytes and recombinant DARC-Fc. 

This project will utilize reagents and techniques in place at the respective labs, provide post-doctoral training in “cutting edge” approaches to vaccine design, and will enable cross-fertilization of techniques between the laboratories.

For more information on the research programs of these and other program faculty, please see Research Interests and Participating Faculty.  To return to the fellowships page click here.