Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice.
Proc Natl Acad Sci U S A
; 118(38)2021 09 21.
Artigo
em Inglês
| MEDLINE | ID: covidwho-1397979
ABSTRACT
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.
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Bases de dados internacionais
Base de dados:
MEDLINE
Assunto principal:
Engenharia de Proteínas
/
Glicoproteína da Espícula de Coronavírus
/
Vacinas contra COVID-19
/
SARS-CoV-2
/
COVID-19
Tópicos:
Vacinas
/
Variantes
Limite:
Animais
/
Humanos
Idioma:
Inglês
Ano de publicação:
2021
Tipo de documento:
Artigo
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