application): Research Proposal: Development of strategies to direct immune responses toward conformation dependent neutralization epitopes is an important component of lentivirus vaccine research. This proposal addresses the hypothesis that dampening of linear immunodominant epitopes of caprine arthritis-encephalitis virus (CAEV) surface envelope glycoprotein (SU) by introduction of N-linked glycosylation sites will enhance cross-reactive neutralizing antibody responses induced by protein immunization. The CAEV model is particularly suitable to address this strategy because the immune response of infected goats is dominated by antibodies directed to linear immunodominant SU epitopes with relatively low titers of mainly type-specific neutralizing antibodies. In addition, previous studies document that (i) conformational crossreactive neutralization epitopes on oligomeric CAE virion-associated SU are exposed on soluble SU, (ii) repeated immunization with native SU induces cross reactive neutralizing antibodies, and (iii) virus neutralization is inhibited by antibodies likely directed to immunodominant linear epitopes.
| Trujillo, Jessie D; Hotzel, Kathy J; Snekvik, Kevin R et al. (2004) Antibody response to the surface envelope of caprine arthritis-encephalitis lentivirus: disease status is predicted by SU antibody isotype. Virology 325:129-36 |
| Trujillo, J D; Kumpula-McWhirter, N M; Hotzel, K J et al. (2004) Glycosylation of immunodominant linear epitopes in the carboxy-terminal region of the caprine arthritis-encephalitis virus surface envelope enhances vaccine-induced type-specific and cross-reactive neutralizing antibody responses. J Virol 78:9190-202 |
