Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1
- Walter Reed Army Institute of Research, United States
- Emory University, United States
- National Institutes of Health, United States
- Duke University School of Medicine, United States
- Mahidol University, Thailand
- AFRIMS, Thailand
- Chiang Mai University, Thailand
- Ministry of Public Health, Thailand
- Fred Hutchinson Cancer Research Center, United States
Abstract
A gene signature previously correlated with mosaic adenovirus 26 vaccine protection in simian immunodeficiency virus (SIV) and SHIV challenge models in non-human primates (NHP). In this report we investigated 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. 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 vaccine efficacy represents a tool both to identify potential mechanisms, as with ADCP here, and to screen novel approaches to accelerate development of new vaccine candidates.
Data availability
All code and data generated or analyzed during this study are included with the manuscript and supporting files. Source data files have been provided for all data used in this study, including CITE-seq and gene expression matrix for all studies are available at figshare 10.6084/m9.figshare.14555958. The RNA-seq gene expression data for RV306 and HVTN 505 studies are available in the National Center for Biotechnology Information Gene Expression Omnibus (GEO) under accession numbers: "GSE181932" and "GS1E181859" respectively. Dataset from GSE181932 can be accessed at URL https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE181932with reviewer token mnyxkcgedbqdnch.Dataset from GSE181859 can be accessed at URL https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE181859with reviewer token etuhyseoxrghxkd.
Article and author information
Author details
Philip K Ehrenberg
Funding
Henry M. Jackson Foundation (W81XWH-07-2-0067)
- Shida Shangguan
- Philip K Ehrenberg
- Aviva Geretz
- Lauren Yum
- Gautam Kundu
- Kelly May
- Eric Lewitus
- Morgane Rolland
- Nelson L Michael
- Sandhya Vasan
- Rasmi Thomas
National Institute of Allergy and Infectious Diseases
- Shida Shangguan
- Philip K Ehrenberg
- Aviva Geretz
- Lauren Yum
- Gautam Kundu
- Eric Lewitus
- Morgane Rolland
- Nelson L Michael
- Sandhya Vasan
- Rasmi Thomas
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1
eLife 10:e69577.
https://doi.org/10.7554/eLife.69577
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