Evidence map›Paper›PMID 34493582›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice.

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 and 34 more

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 99 citations in OpenAlex.

  1. Trial
  2. Pichia-CLM: A language model-based codon optimization pipeline forProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  4. Improving the immunogenicity ofFrontiers in immunology · 2026
    Article
  5. A Brief History of the Pichia pastoris Expression System.Methods in molecular biology (Clifton, N.J.) · 2026
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13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

44 authors at 8 institutions in 1 country.

Neil C DalvieDepartment of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.ORCID 0000-0002-7912-0309
Sergio A Rodriguez-AponteThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Brittany L HartwellThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Lisa H TostanoskiCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.ORCID 0000-0001-9255-5684
Andrew M BiedermannDepartment of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.
Laura E CrowellDepartment of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.
Kawaljit KaurDepartment of Pharmaceutical Chemistry, Vaccine Analytics, and Formulation Center, University of Kansas, Lawrence, KS 66047.
Ozan S KumruDepartment of Pharmaceutical Chemistry, Vaccine Analytics, and Formulation Center, University of Kansas, Lawrence, KS 66047.
Lauren CarterDepartment of Biochemistry, University of Washington, Seattle, WA 98195.
Jingyou YuCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.
Aiquan ChangCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.ORCID 0000-0002-9482-0979
Katherine McMahanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.
Thomas CourantVaccine Formulation Institute, 1228 Plan-Les-Ouates, Geneva, Switzerland.
Celia LebasVaccine Formulation Institute, 1228 Plan-Les-Ouates, Geneva, Switzerland.
Ashley A LemniosThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-6866-6867
Kristen A RodriguesThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-0680-9834
Murillo SilvaThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Ryan S JohnstonThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Christopher A NaranjoThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Mary Kate TraceyThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Joseph R BradyDepartment of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.ORCID 0000-0002-2284-3872
Charles A WhittakerThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-2400-0094
Dongsoo YunThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Natalie BrunetteDepartment of Biochemistry, University of Washington, Seattle, WA 98195.
Jing Yang WangDepartment of Biochemistry, University of Washington, Seattle, WA 98195.ORCID 0000-0002-1511-6976
Carl WalkeyDepartment of Biochemistry, University of Washington, Seattle, WA 98195.
Brooke FialaDepartment of Biochemistry, University of Washington, Seattle, WA 98195.ORCID 0000-0003-0148-5268
Swagata KarBioqual, Inc., Rockville, MD 20850.
Maciel PortoBioqual, Inc., Rockville, MD 20850.
Megan LokBioqual, Inc., Rockville, MD 20850.
Hanne AndersenBioqual, Inc., Rockville, MD 20850.
Mark G LewisBioqual, Inc., Rockville, MD 20850.ORCID 0000-0001-7852-0135
Kerry R LoveDepartment of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.
Danielle L CampThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Judith Maxwell SilvermanBill & Melinda Gates Medical Research Institute, Cambridge, MA 02139.
Harry KleanthousBill & Melinda Gates Foundation, Seattle, WA 98109.
Sangeeta B JoshiDepartment of Pharmaceutical Chemistry, Vaccine Analytics, and Formulation Center, University of Kansas, Lawrence, KS 66047.
David B VolkinDepartment of Pharmaceutical Chemistry, Vaccine Analytics, and Formulation Center, University of Kansas, Lawrence, KS 66047.
Patrice M DuboisVaccine Formulation Institute, 1228 Plan-Les-Ouates, Geneva, Switzerland.ORCID 0000-0002-7128-9396
Nicolas CollinVaccine Formulation Institute, 1228 Plan-Les-Ouates, Geneva, Switzerland.
Neil P KingDepartment of Biochemistry, University of Washington, Seattle, WA 98195.
Dan H BarouchRagon Institute of Massachusetts General Hospital (MGH), MIT, Harvard, Cambridge, MA 02139.
Darrell J IrvineThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-8637-1405
J Christopher LoveDepartment of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139; clove@mit.edu.ORCID 0000-0003-0921-3144
Massachusetts Institute of Technology · USUniversity of Washington · USBeth Israel Deaconess Medical Center · USBioqual · USUniversity of Kansas · USGates Foundation · USRagon Institute of MGH, MIT and Harvard · USHoward Hughes Medical Institute · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9M
Multidisciplinary HIV Training ProgramT32AI007387 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel R. Kuritzkes · 1990 to 2026
$8.8M
NCI NIH HHS P30 CA014051NIAID NIH HHS T32 AI007387
6 · The paper itself

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.

Indexed as

AnimalsAntibodies, ViralAntigens, ViralBinding SitesCOVID-19COVID-19 VaccinesHumansImmunogenicity, VaccineMiceMice, Inbred BALB CModels, MolecularProtein BindingProtein ConformationProtein EngineeringSaccharomycetalesSARS-CoV-2Antibodies, ViralAntigens, ViralCOVID-19 VaccinesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Vaccines, SubunitmanufacturabilityPichia pastorisprotein vaccineSARS-CoV-2

Identifiers

PMID34493582
PMCPMC8463846
OpenAlexW3196466029

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.