Event
CHBE Seminar: Dr. Sheetij Dutta, Walter Reed Army Institute of Research
Friday, April 26, 2024
11:00 a.m.
Room 2108 Chemical and Nuclear Engineering Building
Patricia Lorenzana
301-405-1935
plorenza@umd.edu
Epitope display vaccines based on Tobacco Mosaic Virus VLPs
Abstract: Recent approval of two malaria vaccines RTS,S and R21 for the control of malaria in semi-immune pediatric populations living in Africa is a momentous milestone. Both vaccines elicit high antibody concentrations against the circumsporozoite protein (CSP), but they require at least three vaccinations and an annual booster to sustain protection. There is a need to improve efficacy and durability of malaria vaccines. A next-generation vaccine is being developed by directing the responses to epitopes of structurally defined inhibitory monoclonal antibodies. Small epitopes of monoclonal antibodies require stabilization to elicit a potent immune response. We developed the Epitope Disk Nanoparticle (EDN) to evaluate the feasibility of producing epitope-based vaccines. In a plug-and-play approach epitopes were genetically inserted into an exposed loop of the tobacco mosaic virus monomer; 17 of these monomers self-assembled into a ~20 nm disk shaped VLP. The epitope loop displayed along the outer periphery of the disk, resulted in highly immunogenic presentation to the host immune system. EDN is expressed and purified from E. coli allowing for a relatively low cost of goods. The process development and cGMP manufacture of EDN1 malaria vaccine candidate is currently underway. Use of the EDN platform for targeting emerging bacterial and viral pathogens, as well as neglected diseases is ongoing.
Bio: Currently engaged in the development of next-generation vaccines, Dr. Dutta holds a master's in Biotechnology, University of Pune, India: 1991-1993; Ph.D. in Biochemistry University of Lucknow, India: 1993-1998; National Research Council Post Doctoral Fellow at Walter Reed Army Institute of Research (WRAIR): 1998-2001; Chief, Epitope Mapping Lab, WRAIR: 2001-2010; Chief, Structural Vaccinology, WRAIR: 2010--present. Published over 100 research articles and holds 18 patents on development of vaccines and monoclonal antibodies.
