Proteomics of circulating extracellular vesicles reveals diverse clinical presentations of COVID-19 but fails to identify viral peptides
Gualdrón-López, Melisa (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ayllon-Hermida, Alberto (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Cortés Serra, Núria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Resa-Infante, Patricia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Bech-Serra, Joan-Josep (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Aparici-Herraiz, Iris (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Nicolau Fernández, Marc (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Erkizia, Itziar (IrsiCaixa)
Gutierrez-Chamorro, Lucia (IrsiCaixa)
Marfil, Sílvia (IrsiCaixa)
Pradenas, Edwards (IrsiCaixa)
Ávila Nieto, Carlos (IrsiCaixa)
Cucurull, Bernat (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Montaner-Tarbés, Sergio (Innovex Therapeutics S.L)
Muelas, Magdalena (Hospital Clínic i Provincial de Barcelona)
Sotil, Ruth (Hospital Clínic i Provincial de Barcelona)
Ballana, Ester (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Urrea, Víctor (IrsiCaixa)
Fraile, Lorenzo (Universitat de Lleida)
Montoya, Maria (Centro de Investigaciones Biológicas (Madrid))
Vergara-Alert, Júlia (Universitat Autònoma de Barcelona. Centre de Recerca en Sanitat Animal)
Segalés Coma, Joaquim (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Carrillo, Jorge (IrsiCaixa)
Izquierdo Useros, Nuria (IrsiCaixa)
Blanco, Julià (IrsiCaixa)
Fernandez-Becerra, Carmen (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
De La Torre, Carolina (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Pinazo, Maria-Jesus (Hospital Clínic i Provincial de Barcelona)
Martínez Picado, Francisco Javier (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Del Portillo, Hernando A. (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)

Data:	2024
Resum:	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.
Ajuts:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-00595 Agencia Estatal de Investigación PID2022-139271OB-I00 Agencia Estatal de Investigación CB21/13/00063 European Commission 101095606 European Commission 101057100 Agencia Estatal de Investigación PID2022-142908OB-I00
Nota:	Altres ajuts: Fundació La Marató de TV3 (202120-30-31-32)
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	COVID-19 patients ; SARS-CoV-2 ; Antibody response ; Extracellular vesicles ; Immunocapture (CD9) ; Ganglioside-capture (CD169/Siglec-1) ; Size-exclusion chromatography (SEC) ; Proteomics profiling
Publicat a:	Frontiers in cellular and infection microbiology, Vol. 14 (November 2024) , ISSN 2235-2988

DOI: 10.3389/fcimb.2024.1442743
PMID: 39569406

20 p, 5.6 MB

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