1. Microbiology and Infectious Disease
Download icon

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
Research Article
  • Cited 0
  • Views 592
  • Annotations
Cite this article as: eLife 2021;10:e69577 doi: 10.7554/eLife.69577

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.

Metrics

  • 592
    Page views
  • 89
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Categories and tags

Research organisms

Further reading

    1. Chromosomes and Gene Expression
    2. Microbiology and Infectious Disease

    RNase III-mediated processing of a trans-acting bacterial sRNA and its cis-encoded antagonist

    Sarah Lauren Svensson, Cynthia Mira Sharma
    Research Article

    Bacterial small RNAs (sRNAs) are important post-transcriptional regulators in stress responses and virulence. They can be derived from an expanding list of genomic contexts, such as processing from parental transcripts by RNase E. The role of RNase III in sRNA biogenesis is less well understood despite its well-known roles in rRNA processing, RNA decay, and cleavage of sRNA-mRNA duplexes. Here, we show that RNase III processes a pair of cis-encoded sRNAs (CJnc190 and CJnc180) of the foodborne pathogen Campylobacter jejuni. While CJnc180 processing by RNase III requires CJnc190, In contrast, RNase III processes CJnc190 independent of CJnc180 via cleavage of an intramolecular duplex. We also show that CJnc190 directly represses translation of the colonization factor PtmG by targeting a G-rich ribosome binding site, and uncover that CJnc180 is a cis-acting antagonist of CJnc190, indirectly affecting ptmG regulation. Our study highlights a role for RNase III in sRNA biogenesis and adds cis-encoded RNAs to the expanding diversity of transcripts that antagonize bacterial sRNAs.

    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis

    Andreas Hober et al.
    Research Article Updated

    Reliable, robust, large-scale molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for monitoring the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a scalable analytical approach to detect viral proteins based on peptide immuno-affinity enrichment combined with liquid chromatography-mass spectrometry (LC-MS). This is a multiplexed strategy, based on targeted proteomics analysis and read-out by LC-MS, capable of precisely quantifying and confirming the presence of SARS-CoV-2 in phosphate-buffered saline (PBS) swab media from combined throat/nasopharynx/saliva samples. The results reveal that the levels of SARS-CoV-2 measured by LC-MS correlate well with their correspondingreal-time polymerase chain reaction (RT-PCR) read-out (r = 0.79). The analytical workflow shows similar turnaround times as regular RT-PCR instrumentation with a quantitative read-out of viral proteins corresponding to cycle thresholds (Ct) equivalents ranging from 21 to 34. Using RT-PCR as a reference, we demonstrate that the LC-MS-based method has 100% negative percent agreement (estimated specificity) and 95% positive percent agreement (estimated sensitivity) when analyzing clinical samples collected from asymptomatic individuals with a Ct within the limit of detection of the mass spectrometer (Ct ≤ 30). These results suggest that a scalable analytical method based on LC-MS has a place in future pandemic preparedness centers to complement current virus detection technologies.

    1. Microbiology and Infectious Disease

    The East Asian gut microbiome is distinct from colocalized White subjects and connected to metabolic health

    Qi Yan Ang et al.
    Research Article Updated

    East Asians (EAs) experience worse metabolic health outcomes compared to other ethnic groups at lower body mass indices; however, the potential role of the gut microbiota in contributing to these health disparities remains unknown. We conducted a multi-omic study of 46 lean and obese East Asian and White participants living in the San Francisco Bay Area, revealing marked differences between ethnic groups in bacterial richness and community structure. White individuals were enriched for the mucin-degrading Akkermansia muciniphila. East Asian subjects had increased levels of multiple bacterial phyla, fermentative pathways detected by metagenomics, and the short-chain fatty acid end-products acetate, propionate, and isobutyrate. Differences in the gut microbiota between the East Asian and White subjects could not be explained by dietary intake, were more pronounced in lean individuals, and were associated with current geographical location. Microbiome transplantations into germ-free mice demonstrated stable diet- and host genotype-independent differences between the gut microbiotas of East Asian and White individuals that differentially impact host body composition. Taken together, our findings add to the growing body of literature describing microbiome variations between ethnicities and provide a starting point for defining the mechanisms through which the microbiome may shape disparate health outcomes in East Asians.