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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eLife Sciences Publications Ltd
2021
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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) |
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HIV vaccine transcriptomics single cell CITE-seq vaccine efficacy ADCP Medicine R Science Q Biology (General) QH301-705.5 |
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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 |
work_keys_str_mv |
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