Abstract In late 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged in Wuhan, China. SARS‐CoV‐2 and the disease it causes, coronavirus disease 2019 (COVID‐19), spread rapidly and became a global pandemic in early 2020. SARS‐CoV‐2 spike protein is responsible for viral entry and binds to angiotensin converting enzyme 2 (ACE2) on host cells, making it a major target of the immune system – particularly neutralizing antibodies (nAbs) that are induced by infection or vaccines. Extracellular vesicles (EVs) are small membraned particles constitutively released by cells, including virally‐infected cells. EVs and viruses enclosed within lipid membranes share some characteristics: they are small, sub‐micron particles and they overlap in cellular biogenesis and egress routes. Given their shared characteristics, we hypothesized that EVs released from spike‐expressing cells could carry spike and serve as decoys for anti‐spike nAbs, promoting viral infection. Here, using mass spectrometry and nanoscale flow cytometry (NFC) approaches, we demonstrate that SARS‐CoV‐2 spike protein can be incorporated into EVs. Furthermore, we show that spike‐carrying EVs act as decoy targets for convalescent patient serum‐derived nAbs, reducing their effectiveness in blocking viral entry. These findings have important implications for the pathogenesis of SARS‐CoV‐2 infection in vivo and highlight the complex interplay between viruses, extracellular vesicles, and the immune system that occurs during viral infections.
【저자키워드】 neutralizing antibody, coronavirus, spike, SARS‐CoV‐2, extracellular vesicle, decoy, 【초록키워드】 coronavirus disease, viruses, viral infection, Coronavirus disease 2019, ACE2, mass spectrometry, Pathogenesis, Vaccines, Neutralizing antibodies, angiotensin converting enzyme 2, Infection, Extracellular vesicles, immune system, severe acute respiratory syndrome Coronavirus, virus, angiotensin converting enzyme, viral entry, viral infections, flow cytometry, Spike protein, Novel coronavirus, Particle, COVID‐19, SARS‐CoV‐2, global pandemic, Spread, Characteristics, cells, Wuhan, Effectiveness, membrane, target, targets, in vivo, convalescent patient, cellular, angiotensin, host cells, acute respiratory syndrome, overlap, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, approaches, enzyme, causes, NAbs, complex interplay, SARS‐CoV‐2 infection, biogenesis, EVs, Vesicle, implication, Cell, highlight, Wuhan, China, bind, responsible, the disease, occur, reducing, released, 【제목키워드】 SARS‐CoV‐2, Vesicle,