Engineered SARS-CoV-2 receptor binding domain improves immunogenicity in mice and elicits protective immunity in hamsters
| Autor: | Kristen A Rodrigues, Mary Kate Tracey, Andrew M. Biedermann, Harry Kleanthous, Darrell J. Irvine, Judith M. Silverman, Danielle L Camp, Kerry R. Love, Lauren Carter, Thomas Courant, Neil C. Dalvie, Lisa H. Tostanoski, Megan Lok, J. Christopher Love, Nicolas Collin, Katherine McMahan, Swagata Kar, Hanne Leth Andersen, Ashley A. Lemnios, Charles A. Whittaker, Laura E. Crowell, Celia Lebas, Ozan S. Kumru, Joseph R. Brady, Brittany L. Hartwell, Sergio A. Rodriguez-Aponte, Kawaljit Kaur, David B. Volkin, Murillo Silva, Maciel Porto, Patrice M. Dubois, Dan H. Barouch, Neil P. King, Mark G. Lewis, Aiquan Chang, Sangeeta B. Joshi, Jingyou Yu, Christopher A Naranjo, Ryan S Johnston, Dongsoo Yun |
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| Rok vydání: | 2021 |
| Předmět: |
protein vaccine
Protective immunity Coronavirus disease 2019 (COVID-19) biology SARS-CoV-2 Immunogenicity Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Biological Sciences Virology law.invention Engineering Pichia pastoris Viral entry law Physical Sciences biology.protein Recombinant DNA Subunit vaccines Applied Biological Sciences manufacturability Antibody |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| Popis: | Significance Most of the global population resides in low- and middle-income countries, where current vaccines for COVID-19 remain largely unavailable. For the COVID-19 pandemic, the world will need access to >10 billion doses of vaccines, or more than double the annual volume of vaccines for all other diseases. Many vaccine candidates use the SARS-CoV-2 receptor-binding domain (RBD) antigen. Here, we present an engineered RBD with improved production titers in Pichia pastoris, a yeast commonly used for large-scale, low-cost manufacturing by vaccine manufacturers. The modified RBD also raises an enhanced immune response in mice relative to the Wuhan-Hu-1 sequence used in current candidates. These combined traits make it a promising candidate for next-generation vaccines addressing emerging variants of the virus. Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access. Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing cost. These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples. Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2. Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge. |
| Databáze: | OpenAIRE |
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