A pan-SARS-CoV-2-specific soluble angiotensin-converting enzyme 2-albumin fusion engineered for enhanced plasma half-life and needle-free mucosal delivery
Abstrak
Abstract 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.
Penulis (20)
Sopisa Benjakul
Aina Karen Anthi
Anette Kolderup
Marina Vaysburd
Heidrun Elisabeth Lode
Donna Mallery
Even Fossum
Elisabeth Lea Vikse
Anna Albecka
Aleksandr Ianevski
Denis Kainov
Karine Flem Karlsen
Siri Aastedatter Sakya
Mari Nyquist-Andersen
Torleif Tollefsrud Gjølberg
Morten C Moe
Magnar Bjørås
Inger Sandlie
Leo C James
Jan Terje Andersen
Format Sitasi
Akses Cepat
- Tahun Terbit
- 2023
- Bahasa
- en
- Total Sitasi
- 7×
- Sumber Database
- CrossRef
- DOI
- 10.1093/pnasnexus/pgad403
- Akses
- Open Access ✓