Adaptation-Proof SARS-CoV-2 Vaccine Design

Yashavantha L. Vishweshwaraiah; Brianna Hnath; Brendan RackleyJian WangAbhinay GontuMorgan ChandlerKirill A. AfoninSuresh V. KuchipudiNeil ChristensenNeela H. YennawarNikolay V. Dokholyan

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Adaptation-Proof SARS-CoV-2 Vaccine Design

机译：Adaptation-Proof SARS-CoV-2 Vaccine Design

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface spikeglycoprotein—a major antibody target—is critical for virus entry via engagementof human angiotensin-converting enzyme 2 (ACE2) receptor. Despitesuccesses with existing vaccines and therapies that primarily target thereceptor binding domain (RBD) of the spike protein, the susceptibility of RBDto mutations provides escape routes for the SARS-CoV-2 from neutralizingantibodies. On the other hand, structural conservation in the spike proteincan be targeted to reduce escape mutations and achieve broad protection.Here, candidate stable immunogens are designed that mimic surface featuresof selected conserved regions of spike protein through “epitope grafting,”in which the target epitope topology is presented on diverse heterologousscaffolds that can structurally accommodate the spike epitopes. Structuralcharacterization of the epitope-scaffolds showed stark agreement withcomputational models and target epitopes. The sera from mice immunizedwith engineered designs display epitope-scaffolds and spike binding activity.The utility of the designed epitope-scaffolds in diagnostic applications is alsodemonstrated. Taken all together, this study provides an important methodologyfor targeting the conserved, non-RBD structural motifs of spike proteinfor SARS-CoV-2 epitope vaccine design and demonstrates the potential utilityof “epitope grafting” in rational vaccine design.

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《Advanced functional materials》 |2022年第49期|2206055.1-2206055.12|共12页
作者
Yashavantha L. Vishweshwaraiah; Brianna Hnath; Brendan RackleyJian WangAbhinay GontuMorgan ChandlerKirill A. AfoninSuresh V. KuchipudiNeil ChristensenNeela H. YennawarNikolay V. Dokholyan;
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Department of PharmacologyPenn State College of MedicineHershey, PA 17033-0850, USA;

Department of Veterinary and Biomedical Sciences and The HuckInstitutes of the Life SciencesThe Pennsylvania State UniversityUniversity Park, PA 16802, USA;

Department of ChemistryUniversity of North Carolina at CharlotteCharlotte, NC 28223, USADepartment of Microbiology and ImmunologyPenn State College of MedicineHershey, PA 17033-0850, USAThe Huck Institutes of the Life SciencesThe Pennsylvania State UniversityUniversity Park, PA 16802, USADepartment of PharmacologyPenn State College of MedicineHershey, PA 17033-0850, USA Department of Biochemistry & Molecular BiologyPenn State College of MedicineHershey, PA 17033-0850, USA;

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正文语种英语
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computational designs; ELISA; epitopes; SARS-CoV-2; vaccines;

Adaptation-Proof SARS-CoV-2 Vaccine Design

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