Medical Student Research Fellowship for Summer 2012
Mentor: Dr. Ellen S. Vitetta
Department: Cancer Immunobiology Center
Room number: NB9.210
Mail Code: 8576
Phone number: 214-648-1200
Project title: Peptoid-based vaccines
Human subjects IRB approved project number (where applicable): Not Applicable
Animal subjects IRB approved project number (where applicable): 2008-0142 Testing the immunogenicity of peptoids
Brief Description of Project:
Our vaccine platform is based on synthetic structures called peptoids that are selected by existing (in hand) monoclonal antibodies (MAbs). These MAbs are already known to neutralize the virus to which they bind. Peptoids are similar to peptides but have the R groups attached to the N instead of the C atom and many more R groups (not limited to amino acids) can be attached. They are protease resistant and can be synthesized in large libraries cost-effectively. They can be designed to have many diverse shapes that should fit in the binding sites of the neutralizing MAbs used for screening and hence act as B cell epitope mimetics. They are synthesized on beads that can be directly used for rapid screening.
Broadly neutralizing MAbs against HIV, West Nile virus (WNV) and hepatitis C virus (HCV) will be used in screening peptoid libraries to isolate their B cell epitope mimetics. Peptoids that emerge from the screen will be sequenced, synthesized in bulk and used to determine how well they block the binding of the screening MAb to its viral ligand. The best blockers will be coupled to carrier protein, mixed with adjuvant and used to immunize mice. We have already determined that peptoids are very immunogenic when used in this manner (as haptens). The mice should make antibodies that then recognize both the peptoid and the virus. The sera that do will be tested for neutralizing activity.
Previous Publications with Medical Students: (2006-2012)
Ghetie, M-A., Crank, M., Kufert, S., Pop, I., Vitetta, E.S. Rituximab but not other anti-CD20 antibodies reverses multidrug resistance in two B lymphoma cell lines, blocks the activity of P-glycoprotein (P-gp), and induces P-gp to translocate out of lipid rafts. J Immunother, 29:5, 536-544, 2006.
Wachsmann, M., Pop, L.M., and Vitetta, E.S. Pancreatic Adenocarcinoma: A review of Immunologic Aspects, Journal of Investigative Medicine, In Press, 2011.