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CuMV VLPs Containing the RBM from SARS-CoV-2 Spike Protein Drive Dendritic Cell Activation and Th1 Polarization.

Ana Isabel Sebastião1,2, Daniela Mateus1,2, Mylène A Carrascal3

  • 1Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.

Pharmaceutics
|March 29, 2023
PubMed
Summary

Virus-like particles (VLPs) containing SARS-CoV-2 spike protein motifs mature dendritic cells (DCs) and activate immune pathways. This promotes T cell proliferation, enhancing cellular immunity for effective vaccine design against SARS-CoV-2.

Keywords:
COVID-19SARS-CoV-2adaptive immune responsedendritic cellsmemory T cellvirus-like particles

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Determination of Vaccine Immunogenicity Using Bovine Monocyte-Derived Dendritic Cells
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Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Dendritic cells (DCs) are crucial antigen-presenting cells bridging innate and adaptive immunity.
  • DC interaction with SARS-CoV-2 spike protein is key for immunity against the virus and S protein-based vaccines.

Purpose of the Study:

  • To investigate cellular and molecular events triggered by SARS-CoV-2 spike protein receptor-binding motif in virus-like particles (VLPs) within human monocyte-derived DCs.
  • To understand DC maturation and T cell crosstalk induced by VLPs.

Main Methods:

  • Utilized virus-like particles (VLPs) with SARS-CoV-2 spike protein receptor-binding motif.
  • Studied human monocyte-derived dendritic cells (DCs) and T cell co-cultures.
  • Included Toll-like receptor (TLR) agonists as controls.

Main Results:

  • VLPs enhanced expression of MHC molecules and co-stimulatory receptors on DCs, indicating maturation.
  • DC interaction with VLPs activated the NF-kB pathway, promoting pro-inflammatory cytokine secretion.
  • Co-culture of DCs with T cells led to CD4+ and CD8+ T cell proliferation, with a notable CD4+Tbet+ subset.

Conclusions:

  • VLPs stimulate cellular immunity through DC maturation and T cell polarization towards a type 1 T cell profile.
  • Findings provide insights into DC-mediated immune activation and regulation.
  • This knowledge can aid in designing effective SARS-CoV-2 vaccines.