Researchers used an interdisciplinary approach incorporating phylogenetics, 3D protein modeling, and plasmid design to identify and computationally design an antigen representing the core of most currently known sarbecoviruses.
By Hugo Francisco de SouzaSep 27 2023Reviewed by Danielle Ellis, B.Sc. In a recent study published in Nature Biomedical Engineering, researchers used an interdisciplinary approach incorporating phylogenetics, 3D protein modeling, and plasmid design to identify and computationally design an antigen representing the core of most currently known sarbecoviruses.
Researchers began by acquiring and compiling phylogenetic sequences from all known human and animal Sarbecovirus sequences from the National Center for Biotechnology Information virus database. Based on ACE-2 receptor interaction, two main clades were identified in their analysis - clade 1 viruses that do not interact with the receptor, and clade 2 that do. They focus on the hCoV-19/Wuhan/IVDC-HB-01/2019 strain of SARS-CoV-2 for future antigen development.
For antigen selection and immunogenicity confirmation, researchers used in vivo screening of Bagg albino laboratory mice infected with SARS-CoV-2 RBD as a DNA immunogen. Flow cytometry was used to confirm the cross-reactivity of the designed antigens against spike proteins representative of SAR-CoV-1, SARS-CoV-2, SARS-like coronavirus WIV16, and bat coronavirus RaTG13.
Finally, researchers conducted challenge studies in homozygous K18-hACE-2 transgenic mice. Since most of the human population has been exposed to SARS viruses either via direct environmental contact or vaccination drives against coronavirus disease 2019 , researchers tested the potential of T2_17 as a booster vaccine rather than a prime vaccine. Homozygous K18-hACE-2 transgenic mice were first primed with AZD1222 , the licensed vaccine most commonly used in COVID-19 vaccination globally.
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