Genomic and Immunologic analysis of the Chinese attenuated EIAV vaccine

the infection period. Since the virus undergoes rapid mutation following infection, the adaptive immune response must also evolve to meet this challenge. In order to fully understand the evolution of the T cell response during infection, we synthesized forty-four peptides, spanning the entire surface unit protein (gp90) of EIAV, and monitored the peptide-specific T cells responses both in vivo and in vitro over a six month period following challenge. One inapparent carrier (D64) and four recent EIAV infected ponies were included in this study. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated separately with all 44 peptides. The EIAV gp90 epitopes-specific immune responses in vitro were determined by ELISPOT-IFNg assay. In parallel, all peptides were injected intradermally and punch biopsies were collected for real-time PCR tomonitor the cellular immune responses in vivo. As shown by both in vivo and in vitro assays, two of the four recently infected ponies recognized gp90 peptides three weeks post challenge. Similar to the CMI response to HIV infection, peptide-specific T cell recognition patterns changed over time. While some peptides were recognized throughout the sampling period, other peptides were only recognized at the later time points. Also, the response to some specific peptides disappeared after 6 months post infection. By contrast, peptide recognition by the inapparent carrier (D64) was more stable. The mechanisms responsible for this change remain unclear, but this dynamic shift in the immunodominant epitopes hierarchy in the newly infected horses may be the result of mutations in specific epitopes leading to an escape from T cell recognition. In the inapparent carrier, persistent recognition focusing on the more conserved peptides results in a more effective T cell response where virus replication is tightly controlled. These results indicate that T cell responses evolve during the early stage of EIAV infection. This interaction between virus mutation and T cell evolution needs to be considered when designing vaccines.