Human gamma herpesviruses include Epstein-Barr virus (EBV or HHV- 4) and Kaposi's Sarcoma herpesvirus (KSHV or HHV-8). Both are oncogenic and have a chronic latent phase of infection, which leaves humans hosts infected for life. We hope to adapt the current knowledge of these viruses to develop DNA vaccines. Our purpose is to facilitate the elimination or relative suppression of Kaposi's sarcoma (especially in AIDS patients), as caused by KSHV, and of the latent EBV infection found in normals or expressed in some lymphomas, Hodgkin's disease, nasopharyngeal carcinomas, post-transplant lymphoproliferative disease, and infectious mononucleosis. These are over 150 gene products from which to select the targets for a DNA vaccine, as measured by the number of open reading frames in EBV and KSHV. We plan to begin this project (Specific Aim 1) by constructing DNA vaccines directed against four viral gene products, the TSAs (""""""""tumor specific antigens""""""""): LANA (latency associated nuclear antigen) and v-cyclin form KSHV and LMP-1 ((latent membrane protein) and LMP-2A from EBV. The immunogenicity and optimal vaccination strategy will be evaluated and developed in Balb/c mice (Specific Aim 2), where suppression of the transformed phenotype is expected using appropriately engineered vectors with, the 10(3) cell line. (Additional modifications may be needed for LMP-2A, which is the only one of the four TSAs not known to be oncogenic.) Finally, in preparation for future human studies we will test the DNA vaccines in non-human primates (Specific Aim 3). The suppression of EBV-induced lymphomas by the DNA vaccines will be assessed in Cotton top tamarins. Similarly, the acceleration of KSHV elimination will be assessed in DNA vaccine immunized Rhesus macaques. This experience and the immunologic evaluations performed will hopefully be preparatory for a successful trial of one or more of these gamma herpes virus vaccines in man.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR015577-02
Application #
6494173
Study Section
Special Emphasis Panel (ZRR1)
Project Start
2001-09-01
Project End
2002-08-31
Budget Start
Budget End
Support Year
2
Fiscal Year
2001
Total Cost
$256,079
Indirect Cost
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
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