Open AccessEngineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice
Author(s) -
Neil C. Dalvie,
Sergio A. Rodriguez-Aponte,
Brittany L. Hartwell,
Lisa H. Tostanoski,
Andrew M. Biedermann,
Laura E. Crowell,
Kawaljit Kaur,
Ozan S. Kumru,
Lauren Carter,
Jingyou Yu,
Aiquan Chang,
Katherine McMahan,
Thomas Courant,
Célia Lebas,
Ashley A. Lemnios,
Kristen A. Rodrigues,
Murillo Silva,
Ryan S. Johnston,
Christopher A. Naranjo,
Mary Kate Tracey,
Joseph Brady,
Charles A. Whittaker,
Dongsoo Yun,
Natalie Brunette,
Jing Yang Wang,
Carl Walkey,
Brooke Fiala,
Swagata Kar,
Maciel Porto,
Megan Lok,
Hanné Andersen,
Mark G. Lewis,
Kerry R. Love,
Danielle L. Camp,
Judith M. Silverman,
Harry Kleanthous,
Sangeeta B. Joshi,
David B. Volkin,
Patrice Dubois,
Nicolas Collin,
Neil P. King,
Dan H. Barouch,
Darrell J. Irvine,
J. Christopher Love
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2106845118
Subject(s) - immunogenicity , virology , pichia pastoris , covid-19 , pandemic , biology , population , immunology , computational biology , immune system , medicine , recombinant dna , disease , genetics , infectious disease (medical specialty) , gene , environmental health
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.