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

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 reduce...

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Autores principales: Shida Shangguan, Philip K Ehrenberg, Aviva Geretz, Lauren Yum, Gautam Kundu, Kelly May, Slim Fourati, Krystelle Nganou-Makamdop, LaTonya D Williams, Sheetal Sawant, Eric Lewitus, Punnee Pitisuttithum, Sorachai Nitayaphan, Suwat Chariyalertsak, Supachai Rerks-Ngarm, Morgane Rolland, Daniel C Douek, Peter Gilbert, Georgia D Tomaras, Nelson L Michael, Sandhya Vasan, Rasmi Thomas
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Publicado: eLife Sciences Publications Ltd 2021
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spelling oai:doaj.org-article:81dfbbada87149d49aa3e55c7de541542021-11-29T12:14:20ZMonocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-110.7554/eLife.695772050-084Xe69577https://doaj.org/article/81dfbbada87149d49aa3e55c7de541542021-09-01T00:00:00Zhttps://elifesciences.org/articles/69577https://doaj.org/toc/2050-084XA 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.Shida ShangguanPhilip K EhrenbergAviva GeretzLauren YumGautam KunduKelly MaySlim FouratiKrystelle Nganou-MakamdopLaTonya D WilliamsSheetal SawantEric LewitusPunnee PitisuttithumSorachai NitayaphanSuwat ChariyalertsakSupachai Rerks-NgarmMorgane RollandDaniel C DouekPeter GilbertGeorgia D TomarasNelson L MichaelSandhya VasanRasmi ThomaseLife Sciences Publications LtdarticleHIV vaccinetranscriptomicssingle cellCITE-seqvaccine efficacyADCPMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution DOAJ
collection DOAJ
language EN
topic HIV vaccine
transcriptomics
single cell
CITE-seq
vaccine efficacy
ADCP
Medicine
R
Science
Q
Biology (General)
QH301-705.5
spellingShingle HIV vaccine
transcriptomics
single cell
CITE-seq
vaccine efficacy
ADCP
Medicine
R
Science
Q
Biology (General)
QH301-705.5
Shida Shangguan
Philip K Ehrenberg
Aviva Geretz
Lauren Yum
Gautam Kundu
Kelly May
Slim Fourati
Krystelle Nganou-Makamdop
LaTonya D Williams
Sheetal Sawant
Eric Lewitus
Punnee Pitisuttithum
Sorachai Nitayaphan
Suwat Chariyalertsak
Supachai Rerks-Ngarm
Morgane Rolland
Daniel C Douek
Peter Gilbert
Georgia D Tomaras
Nelson L Michael
Sandhya Vasan
Rasmi Thomas
Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1
description 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.
format article
author Shida Shangguan
Philip K Ehrenberg
Aviva Geretz
Lauren Yum
Gautam Kundu
Kelly May
Slim Fourati
Krystelle Nganou-Makamdop
LaTonya D Williams
Sheetal Sawant
Eric Lewitus
Punnee Pitisuttithum
Sorachai Nitayaphan
Suwat Chariyalertsak
Supachai Rerks-Ngarm
Morgane Rolland
Daniel C Douek
Peter Gilbert
Georgia D Tomaras
Nelson L Michael
Sandhya Vasan
Rasmi Thomas
author_facet Shida Shangguan
Philip K Ehrenberg
Aviva Geretz
Lauren Yum
Gautam Kundu
Kelly May
Slim Fourati
Krystelle Nganou-Makamdop
LaTonya D Williams
Sheetal Sawant
Eric Lewitus
Punnee Pitisuttithum
Sorachai Nitayaphan
Suwat Chariyalertsak
Supachai Rerks-Ngarm
Morgane Rolland
Daniel C Douek
Peter Gilbert
Georgia D Tomaras
Nelson L Michael
Sandhya Vasan
Rasmi Thomas
author_sort Shida Shangguan
title Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1
title_short Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1
title_full Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1
title_fullStr Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1
title_full_unstemmed Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1
title_sort monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against hiv-1
publisher eLife Sciences Publications Ltd
publishDate 2021
url https://doaj.org/article/81dfbbada87149d49aa3e55c7de54154
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