Evidence map›Paper›PMID 34780057›Full record

ArticleBiotechnology and bioengineering2022

Scalable, methanol-free manufacturing of the SARS-CoV-2 receptor-binding domain in engineered Komagataella phaffii.

Neil C Dalvie, Andrew M Biedermann, Sergio A Rodriguez-Aponte, Christopher A Naranjo, Harish D Rao, Meghraj P Rajurkar, Rakesh R Lothe, Umesh S Shaligram, Ryan S Johnston, Laura E Crowell and 4 more

Abstract read
In one paragraph

Article in Biotechnology and bioengineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
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

21 citing papers in PubMed.

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  12. Enabling growth-decoupledFrontiers in bioengineering and biotechnology · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Neil C DalvieDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.ORCID 0000-0002-7912-0309
Andrew M BiedermannDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.ORCID 0000-0002-2090-8118
Sergio A Rodriguez-AponteKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Christopher A NaranjoKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Harish D RaoSerum Institute of India Pvt. Ltd., Pune, India.
Meghraj P RajurkarSerum Institute of India Pvt. Ltd., Pune, India.
Rakesh R LotheSerum Institute of India Pvt. Ltd., Pune, India.
Umesh S ShaligramSerum Institute of India Pvt. Ltd., Pune, India.
Ryan S JohnstonKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Laura E CrowellDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.ORCID 0000-0002-3371-7193
Seraphin CastelinoDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Mary K TraceyKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Charles A WhittakerKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
J Christopher LoveDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.ORCID 0000-0003-0921-3144

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9M
Bill & Melinda Gates Foundation INV-002740Bill & Melinda Gates Foundation INV-006131NCI NIH HHS P30 CA014051NCI NIH HHS P30-CA14051
6 · The paper itself

Abstract

Prevention of COVID-19 on a global scale will require the continued development of high-volume, low-cost platforms for the manufacturing of vaccines to supply ongoing demand. Vaccine candidates based on recombinant protein subunits remain important because they can be manufactured at low costs in existing large-scale production facilities that use microbial hosts like Komagataella phaffii (Pichia pastoris). Here, we report an improved and scalable manufacturing approach for the SARS-CoV-2 spike protein receptor-binding domain (RBD); this protein is a key antigen for several reported vaccine candidates. We genetically engineered a manufacturing strain of K. phaffii to obviate the requirement for methanol induction of the recombinant gene. Methanol-free production improved the secreted titer of the RBD protein by >5X by alleviating protein folding stress. Removal of methanol from the production process enabled to scale up to a 1200 L pre-existing production facility. This engineered strain is now used to produce an RBD-based vaccine antigen that is currently in clinical trials and could be used to produce other variants of RBD as needed for future vaccines.

Indexed as

COVID-19genetic engineeringmicrobial engineeringPichia pastorisrecombinant proteinsubunit vaccine

Identifiers

PMID34780057
PMCPMC8653030

What OpenQuestion holds

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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.