SARS-CoV-2 antigen-carrying extracellular vesicles activate T cell responses in a human immunogenicity model

Sarah E Cummings; Sean P Delaney; Frederic St-Denis Bissonnette; Andrew Stalker; Gauri Muradia; Jelica Mehic; Tyson E Graber; Tommy Alain; Jessie R Lavoie

doi:10.1016/j.isci.2023.108708

SARS-CoV-2 antigen-carrying extracellular vesicles activate T cell responses in a human immunogenicity model

iScience. 2023 Dec 12;27(1):108708. doi: 10.1016/j.isci.2023.108708. eCollection 2024 Jan 19.

Authors

Sarah E Cummings^{1

2}, Sean P Delaney^{1

2}, Frederic St-Denis Bissonnette^{1

2}, Andrew Stalker¹, Gauri Muradia¹, Jelica Mehic¹, Tyson E Graber³, Tommy Alain^{2

3}, Jessie R Lavoie^{1

2}

Affiliations

¹ Centre for Oncology, Radiopharmaceuticals and Research, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada.
² Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
³ Children's Hospital of Eastern Ontario Research Institute, Ottawa, 401 Smyth Road, Ottawa, ON K1H 8L1 Canada.

Abstract

Extracellular vesicles (EVs) are entering the clinical arena as novel biologics for infectious diseases, potentially serving as the immunogenic components of next generation vaccines. However, relevant human assays to evaluate the immunogenicity of EVs carrying viral antigens are lacking, contributing to challenges in translating rodent studies to human clinical trials. Here, we engineered EVs to carry SARS-CoV-2 Spike to evaluate the immunogenicity of antigen-carrying EVs using human peripheral blood mononuclear cells (PBMCs). Delivery of Spike EVs to PBMCs resulted in specific immune cell activation as assessed through T cell activation marker expression. Further, Spike EVs were taken up largely by antigen-presenting cells (monocytes, dendritic cells and B cells). Taken together, this human PBMC-based system models physiologically relevant pathways of antigen delivery, uptake and presentation. In summary, the current study highlights the suitability of using human PBMCs for evaluating the immunogenicity of EVs engineered to carry antigens for infectious disease therapeutics.

Keywords: Immunology; Virology.