tetano
Editor, Senior Moderator
Sci Rep
. 2023 Feb 22;13(1):3103.
doi: 10.1038/s41598-023-30305-8.
Plasminogen activator inhibitor 1 is not a major causative factor for exacerbation in a mouse model of SARS-CoV-2 infection
Takashin Nakayama[SUP] 1 [/SUP], Tatsuhiko Azegami[SUP] 2 3 [/SUP], Maki Kiso[SUP] 4 [/SUP], Masaki Imai[SUP] 4 5 [/SUP], Ryuta Uraki[SUP] 4 5 [/SUP], Kaori Hayashi[SUP] 1 [/SUP], Akihito Hishikawa[SUP] 1 [/SUP], Norifumi Yoshimoto[SUP] 1 [/SUP], Ran Nakamichi[SUP] 1 [/SUP], Erina Sugita-Nishimura[SUP] 1 [/SUP], Eriko Yoshida-Hama[SUP] 1 [/SUP], Yoshihiro Kawaoka[SUP] 4 5 6 [/SUP], Hiroshi Itoh[SUP] 1 [/SUP]
Affiliations
Abstract
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.
. 2023 Feb 22;13(1):3103.
doi: 10.1038/s41598-023-30305-8.
Plasminogen activator inhibitor 1 is not a major causative factor for exacerbation in a mouse model of SARS-CoV-2 infection
Takashin Nakayama[SUP] 1 [/SUP], Tatsuhiko Azegami[SUP] 2 3 [/SUP], Maki Kiso[SUP] 4 [/SUP], Masaki Imai[SUP] 4 5 [/SUP], Ryuta Uraki[SUP] 4 5 [/SUP], Kaori Hayashi[SUP] 1 [/SUP], Akihito Hishikawa[SUP] 1 [/SUP], Norifumi Yoshimoto[SUP] 1 [/SUP], Ran Nakamichi[SUP] 1 [/SUP], Erina Sugita-Nishimura[SUP] 1 [/SUP], Eriko Yoshida-Hama[SUP] 1 [/SUP], Yoshihiro Kawaoka[SUP] 4 5 6 [/SUP], Hiroshi Itoh[SUP] 1 [/SUP]
Affiliations
- PMID: 36813909
- DOI: 10.1038/s41598-023-30305-8
Abstract
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.