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

  1. Shida Shangguan
  2. Philip K Ehrenberg
  3. Aviva Geretz
  4. Lauren Yum
  5. Gautam Kundu
  6. Kelly May
  7. Slim Fourati
  8. Krystelle Nganou-Makamdop
  9. LaTonya D Williams
  10. Sheetal Sawant
  11. Eric Lewitus
  12. Punnee Pitisuttithum
  13. Sorachai Nitayaphan
  14. Suwat Chariyalertsak
  15. Supachai Rerks-Ngarm
  16. Morgane Rolland
  17. Daniel C Douek
  18. Peter Gilbert
  19. Georgia D Tomaras
  20. Nelson L Michael
  21. Sandhya Vasan
  22. Rasmi Thomas  Is a corresponding author
  1. Walter Reed Army Institute of Research, United States
  2. Emory University, United States
  3. National Institutes of Health, United States
  4. Duke University School of Medicine, United States
  5. Mahidol University, Thailand
  6. AFRIMS, Thailand
  7. Chiang Mai University, Thailand
  8. Ministry of Public Health, Thailand
  9. 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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Shida Shangguan

    Walter Reed Army Institute of Research, Silver Spring, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Philip K Ehrenberg

    Walter Reed Army Institute of Research, Silver Spring, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8695-4301
  3. Aviva Geretz

    Walter Reed Army Institute of Research, Silver Spring, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Lauren Yum

    Walter Reed Army Institute of Research, Silver Spring, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Gautam Kundu

    Walter Reed Army Institute of Research, Silver Spring, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Kelly May

    Walter Reed Army Institute of Research, Silver Spring, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Slim Fourati

    Pathology and Laboratory Medicine, Emory University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6609-7587
  8. Krystelle Nganou-Makamdop

    National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. LaTonya D Williams

    Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Sheetal Sawant

    Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Eric Lewitus

    Walter Reed Army Institute of Research, Silver Spring, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Punnee Pitisuttithum

    Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  13. Sorachai Nitayaphan

    AFRIMS, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  14. Suwat Chariyalertsak

    Chiang Mai University, Chiang Mai, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  15. Supachai Rerks-Ngarm

    Ministry of Public Health, Nonthaburi, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  16. Morgane Rolland

    Walter Reed Army Institute of Research, Maryland, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Daniel C Douek

    National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  18. Peter Gilbert

    Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  19. Georgia D Tomaras

    Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  20. Nelson L Michael

    Walter Reed Army Institute of Research, Silver Spring, United States
    Competing interests
    The authors declare that no competing interests exist.
  21. Sandhya Vasan

    Walter Reed Army Institute of Research, Silver Spring, United States
    Competing interests
    The authors declare that no competing interests exist.
  22. Rasmi Thomas

    Walter Reed Army Institute of Research, Silver Spring, United States
    For correspondence
    rthomas@hivresearch.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2116-2418

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.

Reviewing Editor

  1. Mark Marsh, University College London, United Kingdom

Publication history

  1. Received: April 20, 2021
  2. Preprint posted: May 15, 2021 (view preprint)
  3. Accepted: September 16, 2021
  4. Accepted Manuscript published: September 17, 2021 (version 1)
  5. Version of Record published: October 13, 2021 (version 2)

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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  1. Shida Shangguan
  2. Philip K Ehrenberg
  3. Aviva Geretz
  4. Lauren Yum
  5. Gautam Kundu
  6. Kelly May
  7. Slim Fourati
  8. Krystelle Nganou-Makamdop
  9. LaTonya D Williams
  10. Sheetal Sawant
  11. Eric Lewitus
  12. Punnee Pitisuttithum
  13. Sorachai Nitayaphan
  14. Suwat Chariyalertsak
  15. Supachai Rerks-Ngarm
  16. Morgane Rolland
  17. Daniel C Douek
  18. Peter Gilbert
  19. Georgia D Tomaras
  20. Nelson L Michael
  21. Sandhya Vasan
  22. Rasmi Thomas
(2021)
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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