Immunocartography: Charting vaccine-driven immunity by applying single cell proteomics to an in vitro human model

J Immunol Methods. 2021 Aug:495:113083. doi: 10.1016/j.jim.2021.113083. Epub 2021 Jun 3.

Abstract

The ability to measure immunomodulatory effects of a vaccine is crucial for novel vaccine design. While traditional animal models have been effective, a better understanding of the response in humans to new vaccines in pre-clinical development is critical for advancement to clinical trials. A translational methodology that can capture the complexity of a vaccine-driven response in a human model, which does not require human exposure, is needed. Here we have designed a platform that uses fresh human whole blood as a key component to study the adaptive immune memory response to vaccine formulations. The response is monitored by high-parameter single cell analysis using mass cytometry (Helios, CyTOF System), allowing for a rapid, in-depth characterization of antigen specific proliferation and expansion of preexisting memory T cells in concert with an innate adjuvant-driven response. In this work we demonstrate the capability of this platform to characterize biologically relevant changes in the cellular response across memory T-cells, B cells, monocytes, and NK cells, at an unprecedented level of detail. This approach that we call Immunocartography has the potential to transform the way new vaccines can be assessed before and throughout clinical development.

Keywords: Immunomodulation; Mass cytometry; Memory response; Vaccines; Whole blood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects
  • Adjuvants, Immunologic / pharmacology
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / metabolism
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunogenicity, Vaccine*
  • Immunologic Memory / drug effects
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / drug effects*
  • Monitoring, Immunologic*
  • Predictive Value of Tests
  • Proteomics*
  • Single-Cell Analysis*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Workflow

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Diphtheria-Tetanus-acellular Pertussis Vaccines