Multimodal profiling of biostabilized human skin modules reveals a coordinated ecosystem response to injected mRNA-1273 COVID-19 vaccine

Allergy. 2024 Dec;79(12):3341-3359. doi: 10.1111/all.16273. Epub 2024 Aug 19.

Abstract

Background: The field of drug development is witnessing a remarkable surge in the development of innovative strategies. There is a need to develop technological platforms capable of generating human data prior to progressing to clinical trials.

Methods: Here we introduce a new flexible solution designed for the comprehensive monitoring of the natural human skin ecosystem's response to immunogenic drugs over time. Based on unique bioengineering to preserve surgical resections in a long survival state, it allows for the first time a comprehensive analysis of resident immune cells response at both organ and single-cell levels.

Results: Upon injection of the mRNA-1273 COVID-19 vaccine, we characterized precise sequential molecular events triggered upon detection of the exogenous substance. The vaccine consistently targets DC/macrophages and mast cells, regardless of the administration route, while promoting specific cell-cell communications in surrounding immune cell subsets.

Conclusion: Given its direct translational relevance, this approach provides a multiscale vision of genuine human tissue immunity that could pave the way toward the development of new vaccination and drug development strategies.

Keywords: human skin modules; immune response; mRNA vaccine tracking; multiplexed imaging; single‐cell RNA‐Seq.

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273* / immunology
  • COVID-19 Vaccines / administration & dosage
  • COVID-19 Vaccines / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Humans
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mast Cells / immunology
  • SARS-CoV-2* / immunology
  • Skin* / immunology

Substances

  • 2019-nCoV Vaccine mRNA-1273
  • COVID-19 Vaccines