Frontiers in Cellular and Infection Microbiology (Nov 2024)

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

  • Melisa Gualdrón-López,
  • Melisa Gualdrón-López,
  • Alberto Ayllon-Hermida,
  • Alberto Ayllon-Hermida,
  • Núria Cortes-Serra,
  • Núria Cortes-Serra,
  • Patricia Resa-Infante,
  • Patricia Resa-Infante,
  • Patricia Resa-Infante,
  • Patricia Resa-Infante,
  • Joan Josep Bech-Serra,
  • Iris Aparici-Herraiz,
  • Iris Aparici-Herraiz,
  • Marc Nicolau-Fernandez,
  • Marc Nicolau-Fernandez,
  • Itziar Erkizia,
  • Lucia Gutierrez-Chamorro,
  • Silvia Marfil,
  • Edwards Pradenas,
  • Carlos Ávila Nieto,
  • Bernat Cucurull,
  • Sergio Montaner-Tarbés,
  • Magdalena Muelas,
  • Ruth Sotil,
  • Ester Ballana,
  • Ester Ballana,
  • Ester Ballana,
  • Victor Urrea,
  • Lorenzo Fraile,
  • Maria Montoya,
  • Julia Vergara,
  • Julia Vergara,
  • Joaquim Segales,
  • Joaquim Segales,
  • Jorge Carrillo,
  • Jorge Carrillo,
  • Nuria Izquierdo-Useros,
  • Nuria Izquierdo-Useros,
  • Julià Blanco,
  • Julià Blanco,
  • Julià Blanco,
  • Carmen Fernandez-Becerra,
  • Carmen Fernandez-Becerra,
  • Carmen Fernandez-Becerra,
  • Carolina de La Torre,
  • Maria-Jesus Pinazo,
  • Maria-Jesus Pinazo,
  • Javier Martinez-Picado,
  • Javier Martinez-Picado,
  • Javier Martinez-Picado,
  • Javier Martinez-Picado,
  • Javier Martinez-Picado,
  • Hernando A. del Portillo,
  • Hernando A. del Portillo,
  • Hernando A. del Portillo

DOI
https://doi.org/10.3389/fcimb.2024.1442743
Journal volume & issue
Vol. 14

Abstract

Read online

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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