Proteomics of circulating extracellular vesicles reveals diverse clinical presentations of COVID-19 but fails to identify viral peptides

Extracellular vesicles (EVs) released by virus-infected cells have the potential to encapsulate viral peptides, a characteristic that could facilitate vaccine development. Furthermore, plasma-derived EVs may elucidate pathological changes occurring in distal tissues during viral infections. We hypothesized that molecular characterization of EVs isolated from COVID-19 patients would reveal peptides suitable for vaccine development. Blood samples were collected from three cohorts: severe COVID-19 patients (G1), mild/asymptomatic cases (G2), and SARS-CoV-2-negative healthcare workers (G3). Samples were obtained at two time points: during the initial phase of the pandemic in early 2020 (m0) and eight months later (m8). Clinical data analysis revealed elevated inflammatory markers in G1. Notably, non-vaccinated individuals in G1 exhibited increased levels of neutralizing antibodies at m8, suggesting prolonged exposure to viral antigens. Proteomic profiling of EVs was performed using three distinct methods: immunocapture (targeting CD9), ganglioside-capture (utilizing Siglec-1) and size-exclusion chromatography (SEC). Contrary to our hypothesis, this analysis failed to identify viral peptides. These findings were subsequently validated through Western blot analysis targeting the RBD of the SARS-CoV-2 Spike protein's and comparative studies using samples from experimentally infected Syrian hamsters. Furthermore, analysis of the EV cargo revealed a diverse molecular profile, including components involved in the regulation of viral replication, systemic inflammation, antigen presentation, and stress responses. These findings underscore the potential significance of EVs in the pathogenesis and progression of COVID-19.

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Publication Details

Journal
Frontiers in Cellular and Infection Microbiology
Published
2024-11-06
DOI
https://doi.org/10.3389/fcimb.2024.1442743
Citations
2
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
0.47
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Proteomics of circulating extracellular vesicles reveals diverse clinical presentations of COVID-19 but fails to identify viral peptides

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2 citations
Frontiers in Cellular and Infection Microbiology
Extracellular vesicles in disease
0.47
article

Proteomics of circulating extracellular vesicles reveals diverse clinical presentations of COVID-19 but fails to identify viral peptides

Alberto Ayllon-Hermida, Carmen Fernández-Becerra, Sergio Montaner-Tarbés, Nuria Izquierdo‐Useros, Iris Aparici‐Herraiz, Itziar Erkizia, Joan Josep Bech‐Serra, Magdalena Muelas‐Fernandez, María Montoya, Melisa Gualdrón‐López, Sílvia Marfil, Lorenzo Fraile, Hernando A. del Portillo, Ester Ballana, Núria Cortes-Serra, Patricia Resa‐Infante, Edwards Pradenas, Joaquím Segalés, Víctor Urrea, Javier Martínez‐Picado, Julià Blanco, María‐Jesús Pinazo, Jorge Carrillo, Lucía Gutiérrez-Chamorro, Marc Nicolau-Fernandez, Carlos Suárez Nieto, C. de la Torre, Julius Vergara, Bernat Cucurull, Ruth Sotil
article en
2 citations

Abstract

Extracellular vesicles (EVs) released by virus-infected cells have the potential to encapsulate viral peptides, a characteristic that could facilitate vaccine development. Furthermore, plasma-derived EVs may elucidate pathological changes occurring in distal tissues during viral infections. We hypothesized that molecular characterization of EVs isolated from COVID-19 patients would reveal peptides suitable for vaccine development. Blood samples were collected from three cohorts: severe COVID-19 patients (G1), mild/asymptomatic cases (G2), and SARS-CoV-2-negative healthcare workers (G3). Samples were obtained at two time points: during the initial phase of the pandemic in early 2020 (m0) and eight months later (m8). Clinical data analysis revealed elevated inflammatory markers in G1. Notably, non-vaccinated individuals in G1 exhibited increased levels of neutralizing antibodies at m8, suggesting prolonged exposure to viral antigens. Proteomic profiling of EVs was performed using three distinct methods: immunocapture (targeting CD9), ganglioside-capture (utilizing Siglec-1) and size-exclusion chromatography (SEC). Contrary to our hypothesis, this analysis failed to identify viral peptides. These findings were subsequently validated through Western blot analysis targeting the RBD of the SARS-CoV-2 Spike protein's and comparative studies using samples from experimentally infected Syrian hamsters. Furthermore, analysis of the EV cargo revealed a diverse molecular profile, including components involved in the regulation of viral replication, systemic inflammation, antigen presentation, and stress responses. These findings underscore the potential significance of EVs in the pathogenesis and progression of COVID-19.

Frontiers in Cellular and Infection MicrobiologyVol. 14
Universitat de Vic - Universitat Central de Catalunya (ES), Institució Catalana de Recerca i Estudis Avançats (ES), Universitat de Lleida (ES), Instituto de Salud Carlos III (ES), IrsiCaixa (ES), Josep Carreras Leukaemia Research Institute (ES), Centre de Recerca en Sanitat Animal (ES), Hospital Clínic de Barcelona (ES), Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES), Centro de Investigaciones Biológicas Margarita Salas (ES), Barcelona Institute for Global Health (ES), Universitat de Barcelona (ES)
Good health and well-being
Openalex Percentile: Top 34%
Extracellular vesicles in disease
0.47
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