Plasminogen activator inhibitor 1 is not a major causative factor for exacerbation in a mouse model of SARS-CoV-2 infection

Takashin Nakayama, Tatsuhiko Azegami, Maki Kiso, Masaki Imai, Ryuta Uraki, Kaori Hayashi, Akihito Hishikawa, Norifumi Yoshimoto, Ran Nakamichi, Erina Sugita-Nishimura, Eriko Yoshida-Hama, Yoshihiro Kawaoka, Hiroshi Itoh

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global pandemic. Although several vaccines targeting SARS-CoV-2 spike proteins protect against COVID-19 infection, mutations affecting virus transmissibility and immune evasion potential have reduced their efficacy, leading to the need for a more efficient strategy. Available clinical evidence regarding COVID-19 suggests that endothelial dysfunction with thrombosis is a central pathogenesis of progression to systemic disease, in which overexpression of plasminogen activator inhibitor-1 (PAI-1) may be important. Here we developed a novel peptide vaccine against PAI-1 and evaluated its effect on lipopolysaccharide (LPS)-induced sepsis and SARS-CoV-2 infection in mice. Administration of LPS and mouse-adapted SARS-CoV-2 increased serum PAI-1 levels, although the latter showed smaller levels. In an LPS-induced sepsis model, mice immunized with PAI-1 vaccine showed reduced organ damage and microvascular thrombosis and improved survival compared with vehicle-treated mice. In plasma clot lysis assays, vaccination-induced serum IgG antibodies were fibrinolytic. However, in a SARS-CoV-2 infection model, survival and symptom severity (i.e., body weight reduction) did not differ between vaccine- and vehicle-treated groups. These results indicate that although PAI-1 may promote the severity of sepsis by increasing thrombus formation, it might not be a major contributor to COVID-19 exacerbation.

本文言語English
論文番号3103
ジャーナルScientific reports
13
1
DOI
出版ステータスPublished - 2023 12月

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