Myeloid cells are transcriptionally distinct between RhCMV/SIV vaccinated rhesus macaques protected from SIV and unvaccinated SIV-infected animals.
The 68-1 rhesus cytomegalovirus (RhCMV) vector which expresses Simian Immunodeficiency Virus (SIV) genes (Gag/Tat/Nef/5-Pol) is effective in controlling and clearing SIV in rhesus macaques and the human ortholog vector is a vaccine candidate for the prevention of HIV.  Currently the RhCMV/SIV vaccine is only effective in ~55% (referred to as protected animals) of Rhesus Macaques.  A previous study by Barrenäs et al., 2021, showed that significant gene expression changes in a key set of IL-15 linked genes was correlated with a protection outcome. To further our understanding of the transcriptomic state if cells in protected animals and mechanisms of protection induced by the RhCMV vaccine we performed single cell RNA-sequencing on PBMCs from protected, non-protected and unvaccinated animals at longitudinal time points post SIV challenge. We identified monocytes, CD8 T cells and NK cells were primarily responsible for expression of genes in the IL-15 enriched protective signature. Myeloid cells were transcriptionally distinct 1) from all other cell types, 2) between nonprotected and protected vaccinated RMs and 3) between protected and unvaccinated SIV-infected animals.  Specifically, transcriptomics indicated that myeloid cells were more activated and mature in protected animals by the vaccine at pre-challenge and post-challenge time points. This suggests that the transcriptional state of myeloid cells is essential in eliciting a protection outcome and could be used to determine whether an animal will be protected after vaccination. Overall design: Two cohorts of 15 Rhesus macaques (RM) were administered the 68-1 RhCMV/SIV vector expressing SIV Gag, Rev, Tat and 5-Pol either orally or subcutaneously. A homologous boost was given 18 weeks later.  A third cohort of 15 RMs received a modified 68-1.2 RhCMV/SIV vector expressing the same SIV proteins.  PBMCs were collect at baseline (prior to vaccination), pre-challenge (day 595 after vaccination and right before challenge with SIV) and 28, 56,84, and 140 days post SIV challenge.