Medical Student Research Fellowship for Summer 2009

Mentor: Dr. Ellen Vitetta
Department: Cancer Immunobiology Center
Room number: NB9.210
Mail Code: 8576
Phone number: 214-648-1200
E-mail: ellen.vitetta@utsouthwestern.edu
Project title: Antibody response to intradermal administration of RiVax, a ricin vaccine
Student: Theresa Vo

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable): APN# 0034-06-28

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Brief Description of Project:
We have developed a safe and effective vaccine against ricin toxin. The vaccine (RiVax) protects mice from ricin delivered by injection, by gastric gavage and by aerosol. It elicited antibody responses in rabbits and human volunteers. In all case the vaccine was administered intramuscularly. We are now trying to determine if the intradermal route is as effective as the intramuscular route. Mice have been immunized via both routes and are being checked for antibody levels and protection against ricin challenge. We have a large number of sera which we need to evaluate for both total and protective antibodies. The best way to measure antibody levels is ELISA (enzyme linked immunosorbent assay) or RIA (radio immunoassay). These antibodies may not always be neutralizing, therefore it is also important to use cell based assays to determine the levels of neutralizing antibodies in the serum. Specifically, you will be looking for the presence of antibodies that are specific for our ricin vaccine, RiVax, using RIA.

The student will be working with Praveena Selvaduray to determine the titers of RiVax- specific total and protective antibodies in the sera of vaccinated mice. Specifically, she will be comparing the antibody titers of mice given vaccine either by intramuscular injection or intradermal injection in order to determine if there are any immunological benefits to intradermal RiVax administration.

Previous Research Activities or Publications with Medical Students: (2005-2009)

Vitetta, E.S., Smallshaw, J.E., Coleman, E., Jafri, H., Foster, C., Munford, R., and Schindler, J. A pilot clinical trial of a recombinant ricin vaccine in normal humans. PNAS 103:7 2268-2273, 2006.

Wang, S., Coleman, E.J., Pop, L.M., Brooks, K.J., Vitetta, E.S., Niederkorn, J.Y. Effect of an Anti-CD54 (ICAM-1) Monoclonal Antibody (UV3) on the Growth of Human Uveal Melanoma Cells Transplanted Heterotopically and Orthotopically in SCID Mice. Int. J. Cancer, 118:932-941, 2005.

Coleman, E.J., Brooks, K.J., Smallshaw, J.E., Vitetta,E.S. The Fc portion of UV3, an anti-CD54 monoclonal antibody, is critical for its anti-tumor activity in SCID mice with human multiple myeloma or lymphoma cell lines. J Immunotherapy, 29(5)489-498, 2006.

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.

Chakravarty, P., Marches, P., Zimmerman, N.S., Swafford, A.D.E., Bajaj, P., Musselman, I.H., Pantano, P., Draper, R., and Vitetta, E.S. Thermal Ablation of tumor cells with antibody-funcationalized single-walled carbon nanotubes. PNAS, 105: 8697-8702, 2008

Brooks, K., Coleman, E., and Vitetta, E. The antitumor activity of an anti-CD54 antibody in SCID mice xenografted with human breast, prostate, non-small cell lung, and pancreatic tumor cell lines. Int J of Cancer,123:2438-2445, 2008.

Marches, R., Chakravarty, P., Musselman, IH, Bajaj, P., Azad, RN., Pantano, P., Draper, RK, and Vitetta, ES. Specific Thermal Ablation of Tumor Cells using Monoclonal Antbodies Covalenty Coupled to Single-Walled Carbon Nanotubes. Int J of Cancer, submitted, 2009.