A pan-SARS-CoV-2-specific soluble angiotensin-converting enzyme 2-albumin fusion engineered for enhanced plasma half-life and needle-free mucosal delivery.
Sopisa BenjakulAina Karen AnthiAnette KolderupMarina VaysburdHeidrun Elisabeth LodeDonna L MalleryEven FossumElisabeth Lea VikseAnna AlbeckaAleksandr IanevskiDenis E KainovKarine Flem KarlsenSiri Aastedatter SakyaMari Nyquist-AndersenTorleif Tollefsrud GjølbergMorten C MoeMagnar BjøråsInger SandlieLeo C JamesJan Terje AndersenPublished in: PNAS nexus (2023)
Immunocompromised patients often fail to raise protective vaccine-induced immunity against the global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Although monoclonal antibodies have been authorized for clinical use, most have lost their ability to potently neutralize the evolving Omicron subvariants. Thus, there is an urgent need for treatment strategies that can provide protection against these and emerging SARS-CoV-2 variants to prevent the development of severe coronavirus disease 2019. Here, we report on the design and characterization of a long-acting viral entry-blocking angiotensin-converting enzyme 2 (ACE2) dimeric fusion molecule. Specifically, a soluble truncated human dimeric ACE2 variant, engineered for improved binding to the receptor-binding domain of SARS-CoV-2, was fused with human albumin tailored for favorable engagement of the neonatal fragment crystallizable receptor (FcRn), which resulted in enhanced plasma half-life and allowed for needle-free transmucosal delivery upon nasal administration in human FcRn-expressing transgenic mice. Importantly, the dimeric ACE2-fused albumin demonstrated potent neutralization of SARS-CoV-2 immune escape variants.
Keyphrases
- sars cov
- angiotensin converting enzyme
- respiratory syndrome coronavirus
- angiotensin ii
- endothelial cells
- coronavirus disease
- induced pluripotent stem cells
- end stage renal disease
- pluripotent stem cells
- ultrasound guided
- high glucose
- ejection fraction
- social media
- chronic kidney disease
- newly diagnosed
- early onset
- oxidative stress
- extracorporeal membrane oxygenation
- smoking cessation
- diabetic rats
- ulcerative colitis
- patient reported outcomes
- chronic rhinosinusitis