Functional genomic analysis of the 68-1 RhCMV-Mycobacteria tuberculosis vaccine reveals an IL-15 response signature that is conserved with vector attenuation
Here we conducted a bulk RNA-seq analysis of whole blood samples collected from RMs administered with RhCMV vector vaccines using a prime-boost strategy. Two vaccines were used in this study, including 68-1 RhCMV/TB-6Ag (encoding 6 Mtb protein immunogens) and its attenuated variant, 68-1 RhCMV/?pp71-TB-6Ag (a cell to cell spread-deficient vaccine vector lacking the Rh110 gene encoding the pp71 tegument protein). Overall design: To examine the differences in the vaccine signatures between RhCMV/TB vaccines, we conducted a functional genomic analysis of whole blood collected from immunized rhesus macaques (RMs; Macaca mulatta) using bulk RNA sequencing (RNA-seq). A total of 24 RMs (males and females) were randomized and assigned to one of two vaccine groups (n=12 per group). Animals received a prime-boost vaccine regimen of 68-1 RhCMV/TB-6Ag (n=12) or 68-1 RhCMV/?pp71-TB-6Ag vector (n=12) spaced 14 weeks apart that was followed by a second boost administered 92 weeks later (Figure 1a, Table S1). Four RMs of 68-1 RhCMV/?pp71-TB-6Ag group were not included for the further transcriptional analyses due to lack of second boost data. Whole blood samples collected at pre-vaccination day 0 (D0) and 15 time points following prime immunization were processed for bulk RNA-seq analyses.