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Functional avidity of T cells is a critical determinant for clearing viral infection and eliminating tumor. Understanding how functional avidity is maintained in T cells is imperative for immunotherapy. However, studies systematically characterize T cell with high functional avidity induced  in vivo  are still lacking. Previously, we and others found vaccinia vectored vaccine (VACV) induced antigen-specific CD8 +  T cells with relatively high functional avidity to those from DNA vaccine. Herein, we used functional, immune phenotyping and transcriptomic studies to define the immune signature of these CD8 +  T cells with high functional avidity. Antigen-specific CD8 +  T cells induced by VACV executed superior  in vivo  killing activity and displayed a distinct transcriptional profile, whereas no significantly differences were found in composition of memory sub-populations and cytokine poly-functionality. Transcriptional analyses revealed unique features of VACV induced CD8 +  T cells in several biological processes, including transport, cell cycle, cell communication and metabolic processes. In summary, we characterize CD8 +  T cells of high functional avidity induced  in vivo  by VACV, which not only improves our understanding of adaptive T cell immunity in VACV vaccination, but also provides clues to modulate functional avidity of CD8 +  T cells for T cell based immunotherapy.

Immune Signature of Enhanced Functional Avidity CD8+ T Cells in vivo Induced by Vaccinia Vectored Vaccine