Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1.

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Shangguan, S; Ehrenberg, PK; Geretz, A; Yum, L; Kundu, G; May, K; Fourati, S; Nganou-Makamdop, K; Williams, LD; Sawant, S; Lewitus, E; Pitisuttithum, P; Nitayaphan, S; Chariyalertsak, S; Rerks-Ngarm, S; Rolland, M; Douek, DC; Gilbert, P; Tomaras, GD; Michael, NL; Vasan, S; Thomas, R

Published Date

  • September 17, 2021

Published In

Volume / Issue

  • 10 /

PubMed ID

  • 34533134

Pubmed Central ID

  • PMC8514236

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.69577


  • eng

Conference Location

  • England