Mucosal innate gene signature associated with a mucosal SHIV vaccine and reduced SHIV risk in vaccinated macaques

An orally delivered HIV vaccine, which is composed of nanoparticles containing a full-length gp120-CD4 single chain (FLSC) fusion construct plus MVA and molecular adjuvants, has demonstrated 44% vaccine efficacy (p = 0.028) against repeated low-dose intrarectal challenge of rhesus macaques with SHIVSF162P4. From our previous study, we found that the innate immune responses in the rectal mucosa might contribute significantly to the protection. Since the vaccine was administered mucosally, it is critical to evaluate the innate responses in the rectal mucosa. To investigate the possible correlates of protection, we isolated total RNA from the rectal single-cell suspension and ran bulk RNAseq analysis. We distinguished the differentially expressed genes (DEGs) induced by the vaccination and found that gut metabolic pathways, extracellular matrix and antimicrobial humoral responses were altered by mucosal HIV vaccine. We further assessed the genes that were correlated with the number of challenges needed for the animals to be infected. We observed that cytoskeleton genes such as fibronectin 1, Interleukin-4 and Interleukin-13 signaling, O-linked glycosylation were among the gene signatures that inversely correlated with viral infection risk . These data provide key information on the potential biomarkers to predict the outcome of HIV vaccines and shed light on possible protection mechanisms of mucosal HIV vaccines. Overall design: RNA-seq profiling of colorectal tissue extracted from rhesus macaques before and after treatement with vaccine.