Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response.

Journal: Frontiers in immunology
PMID: 34777332

Abstract

Vaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests that a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine and that a wide range of antibody levels were elicited after three doses. The immune mechanisms responsible for this vaccine response variability is unclear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) correlated with the immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline - an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. To explore this correlation further, genes expressed in these mDC subsets were used for feature selection prior to the construction of predictive models using supervised canonical correlation machine learning. The resulting models showed an improved correlation with serum antibody titers in response to full vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their "dispositional endotype" at pre-vaccination baseline, could dictate response to vaccination.

Authors

  • Brian D Aevermann
    J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA, 92037, USA.
  • Casey P Shannon
    PROOF Centre of Excellence, Vancouver, BC, Canada. casey.shannon@hli.ubc.ca.
  • Mark Novotny
    J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA, 92037, USA.
  • Rym Ben-Othman
    Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
  • Bing Cai
    Department of Anesthesiology, Xuanwu Hospital, Capital Medical University Beijing, China.
  • Yun Zhang
    Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.
  • Jamie C Ye
    Prevention of Organ Failure (PROOF) Centre of Excellence, St. Paul's Hospital, Vancouver, BC, Canada.
  • Michael S Kobor
    Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
  • Nicole Gladish
    Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
  • Amy Huei-Yi Lee
    Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
  • Travis M Blimkie
    Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
  • Robert E Hancock
    Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
  • Alba Llibre
    Translational Immunology Lab, Institut Pasteur, Paris, France.
  • Darragh Duffy
    Translational Immunology Lab, Institut Pasteur, Paris, France.
  • Wayne C Koff
    Human Vaccines Project, New York, NY, United States.
  • Manish Sadarangani
    Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
  • Scott J Tebbutt
    PROOF Centre of Excellence, Vancouver, BC, Canada.
  • Tobias R Kollmann
    Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
  • Richard H Scheuermann
    J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA, 92037, USA. RScheuermann@jcvi.org.

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