TY - JOUR TI - Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1 AU - Shangguan, Shida AU - Ehrenberg, Philip K AU - Geretz, Aviva AU - Yum, Lauren AU - Kundu, Gautam AU - May, Kelly AU - Fourati, Slim AU - Nganou-Makamdop, Krystelle AU - Williams, LaTonya D AU - Sawant, Sheetal AU - Lewitus, Eric AU - Pitisuttithum, Punnee AU - Nitayaphan, Sorachai AU - Chariyalertsak, Suwat AU - Rerks-Ngarm, Supachai AU - Rolland, Morgane AU - Douek, Daniel C AU - Gilbert, Peter AU - Tomaras, Georgia D AU - Michael, Nelson L AU - Vasan, Sandhya AU - Thomas, Rasmi A2 - Marsh, Mark A2 - Ojala, Päivi M A2 - Franchini, Genoveffa VL - 10 PY - 2021 DA - 2021/09/17 SP - e69577 C1 - eLife 2021;10:e69577 DO - 10.7554/eLife.69577 UR - https://doi.org/10.7554/eLife.69577 AB - A gene signature was previously found to be correlated with mosaic adenovirus 26 vaccine protection in simian immunodeficiency virus and simian-human immunodeficiency virus challenge models in non-human primates. In this report, we investigated the presence of this signature as a correlate of reduced risk in human clinical trials and potential mechanisms of protection. The absence of this gene signature in the DNA/rAd5 human vaccine trial, which did not show efficacy, strengthens our hypothesis that this signature is only enriched in studies that demonstrated protection. This gene signature was enriched in the partially effective RV144 human trial that administered the ALVAC/protein vaccine, and we find that the signature associates with both decreased risk of HIV-1 acquisition and increased vaccine efficacy (VE). Total RNA-seq in a clinical trial that used the same vaccine regimen as the RV144 HIV vaccine implicated antibody-dependent cellular phagocytosis (ADCP) as a potential mechanism of vaccine protection. CITE-seq profiling of 53 surface markers and transcriptomes of 53,777 single cells from the same trial showed that genes in this signature were primarily expressed in cells belonging to the myeloid lineage, including monocytes, which are major effector cells for ADCP. The consistent association of this transcriptome signature with VE represents a tool both to identify potential mechanisms, as with ADCP here, and to screen novel approaches to accelerate the development of new vaccine candidates. KW - HIV vaccine KW - transcriptomics KW - single cell KW - CITE-seq KW - vaccine efficacy KW - ADCP JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -