ATAC-seq profiling in CD14+ cells isolated from rhesus macaques vaccinated with V1-deleted DNA/ALVAC/gp120 vaccine [study 2]

We analyzed innate and adaptive immune responses elicited by the V1-deleted DNA/ALVAC/gp120/alum vaccine in non-human primates. Following SIVmac251 challenge exposure, we observed reduced risk of SIV acquisition comparing vaccinated animals to controls, confirming th ability of this vaccine strategy in decreasing the risk of SIV acquisition against vaginal exposure. Transcriptome and chromatin accessibility in CD14+ cells were analyzed by RNA-seq and ATAC-seq. Epigenetic reprogramming in CD14+ cells of the cyclic AMP/CREB pathway correlated with vaccine efficacy. The efficacy of V1-delted DNA/ALVAC/gp120/alum vaccine, based on V2-specific antibodies mediating apoptosis of infected cells (V2-ADCC), is complemented by efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment of apoptotic cells by CD14+ monocytes. Our data support the protective role for CREB1 expression in monocytes and posit that efferocytosis, through the prompt and effective removal of apoptotic infected cells, contributes to vaccine efficacy by decreasing inflammation and maintaining tissue homeostasis. Overall design: Twelve juvenile (average age 3.91 years, 0.155 SD), female macaques were enrolled in the study. All twelve macaques were immunized twice with V1-deleted DNA-SIV at weeks 0 and 4. At weeks 8 and 12 all macaques were boosted with intramuscular inoculations of 10^8 Plaque Forming Units (PFU) of recombinant ALVAC (vCP2432). At week 12, vaccinated macaques also received 400 µg of v1-delted SIVmac251–M766 protein formulated in alum Alhydrogel. The isolation of CD14+ cells was performed from freshly isolated PBMCs collected at weeks 13. The chromatin accessibility of monocyte population was assessed by Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq).