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| Status |
Public on Sep 09, 2021 |
| Title |
Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice |
| Organism |
Komagataella phaffii |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Two gene expression analysis experiments where various numbers of replicates of yeast cells expressing SARS-Cov2 receptor binding domain (RBD) transgenes were compared to cells expressing the P8 control transgene. The exp020821 experiment compares wild type or engineered RBD to controls. The exp031020 compares wild type RBD to controls.
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| Contributor(s) |
Dalvie NC, Rodriguez-Aponte SA, Hartwell BL, Tostanoski LH, Biedermann AM, Crowell LE, Kaur K, Kumru OS, Carter L, Yu J, Chang A, McMahan K, Courant T, Lebas C, Lemnios AA, Rodrigues KA, Silva M, Johnston RS, Naranjo CA, Tracey MK, Brady JR, Whittaker CA, Yun D, Kar S, Porto M, Lok M, Andersen H, Lewis MG, Love KR, Camp DL, Silverman JM, Kleanthous H, Joshi SM, Volkin DB, Dubois PM, Collin N, King NP, Barouch DH, Irvine DJ, Love JC |
| Citation(s) |
33688647, 34493582 |
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| Submission date |
Apr 14, 2021 |
| Last update date |
Nov 03, 2021 |
| Contact name |
Charles Arthur Whittaker |
| E-mail(s) |
charliew@mit.edu
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| Organization name |
Koch Institute
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| Street address |
77 Mass Ave 76-189
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02152 |
| Country |
USA |
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| Platforms (1) |
| GPL30002 |
Illumina MiSeq (Komagataella phaffii) |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA721898 |
| SRA |
SRP314811 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE172054_dalvie020821_intCt.txt.gz |
69.6 Kb |
(ftp)(http) |
TXT |
| GSE172054_dalvie020821_l2cpm.txt.gz |
161.4 Kb |
(ftp)(http) |
TXT |
| GSE172054_dalvie031020_intCt.txt.gz |
82.1 Kb |
(ftp)(http) |
TXT |
| GSE172054_dalvie031020_l2cpm.txt.gz |
230.0 Kb |
(ftp)(http) |
TXT |
| GSE172054_phaffi_plus_transgenes_020821.fa.gz |
2.3 Mb |
(ftp)(http) |
FA |
| GSE172054_phaffi_plus_transgenes_031020.fa.gz |
2.3 Mb |
(ftp)(http) |
FA |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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