The eradication of lentivirus infections remains an extremely difficult challenge. Caprine arthritis encephalitis virus (CAEV) offers an attractive, although difficult system for understanding the pathogenesis and treatment of lentivirus induced diseases of animals and perhaps those of humans. Dr. Beyer proposes a vaccine development strategy that is based on enhancing cell mediated immune responses to CAEV infection by stimulating type 1 responses, that is those mediated by type 1 (Th1) T lymphocytes. This based on findings that diseased goats have high virus titers yet mount a vigorous humoral immune response to CAEV antigens including the production of neutralizing antibodies directed against env gene products. In contrast, Dr. Beyer, and his mentor, Dr. Cheevers, have observed that asymptomatic CAEV infected goats display high CD4+ lymphoid proliferative responses and low virus titers. Vaccination will be accomplished by injecting an interferon gamma (IFN- gamma) expression vector DNA into goats to prime antigen-specific type 1 T cells and then injecting DNA of a CAEV env gene expression vector into the same animals. The goats will then be challenged with CAEV and analyzed for virus replication and development of symptoms.
Cheevers, W P; Beyer, J C; Hotzel, I (2001) Plasmid DNA encoding caprine interferon gamma inhibits antibody response to caprine arthritis-encephalitis virus (CAEV) surface protein encoded by a co-administered plasmid expressing CAEV env and tat genes. Vaccine 19:3209-15 |
Cheevers, W P; Hotzel, I; Beyer, J C et al. (2000) Immune response to caprine arthritis-encephalitis virus surface protein induced by coimmunization with recombinant vaccinia viruses expressing the caprine arthritis-encephalitis virus envelope gene and caprine interleukin-12. Vaccine 18:2494-503 |
Beyer, J C; Stich, R W; Hoover, D S et al. (1998) Cloning and expression of caprine interferon-gamma. Gene 210:103-8 |
Cheevers, W P; Beyer, J C; Knowles, D P (1997) Type 1 and type 2 cytokine gene expression by viral gp135 surface protein-activated T lymphocytes in caprine arthritis-encephalitis lentivirus infection. J Virol 71:6259-63 |