Simian Immunodeficiency Virus SIVmac239Δnef Vaccination Elicits Different Tat28-35SL8-Specific CD8+ T-Cell Clonotypes Compared to a DNA Prime/Adenovirus Type 5 Boost Regimen in Rhesus Macaques

Different human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccine vectors expressing the same viral antigens can elicit disparate T-cell responses. Within this spectrum, replicating variable vaccines, like SIVmac239 Delta nef, appear to generate particularly efficacious CD8(+) T-cell responses. Here, we sequenced T-cell receptor beta-chain (TRB) gene rearrangements from immunodominant Mamu-A*01-restricted Tat(28-35)SL8-specific CD8(+) T-cell populations together with the corresponding viral epitope in four rhesus macaques during acute SIVmac239 Delta nef infection. Ultradeep pyrosequencing showed that viral variants arose with identical kinetics in SIVmac239 Delta nef and pathogenic SIVmac239 infection. Furthermore, distinct Tat(28-35)SL8-specific T-cell receptor (TCR) repertoires were elicited by SIVmac239 Delta nef compared to those observed following a DNA/Ad5 prime-boost regimen, likely reflecting differences in antigen sequence stability.