Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul;120(7):1746-1761.
doi: 10.1002/bit.28387. Epub 2023 Mar 29.

A CHO stable pool production platform for rapid clinical development of trimeric SARS-CoV-2 spike subunit vaccine antigens

Simon Joubert  1 , Matthew Stuible  1 , Simon Lord-Dufour  1 , Linda Lamoureux  1 , François Vaillancourt  1 , Sylvie Perret  1 , Manon Ouimet  1 , Alex Pelletier  1 , Louis Bisson  1 , Rohan Mahimkar  1 , Phuong Lan Pham  1 , Helene L Ecuyer-Coelho  1 , Marjolaine Roy  1 , Robert Voyer  1 , Jason Baardsnes  1 , Janelle Sauvageau  2 , Frank St-Michael  2 , Anna Robotham  2 , John Kelly  2 , Andrea Acel  1 , Joseph D Schrag  1 , Majida El Bakkouri  1 , Yves Durocher  1   3
Affiliations

A CHO stable pool production platform for rapid clinical development of trimeric SARS-CoV-2 spike subunit vaccine antigens

Simon Joubert et al. Biotechnol Bioeng. 2023 Jul.

Abstract

Protein expression from stably transfected Chinese hamster ovary (CHO) clones is an established but time-consuming method for manufacturing therapeutic recombinant proteins. The use of faster, alternative approaches, such as non-clonal stable pools, has been restricted due to lower productivity and longstanding regulatory guidelines. Recently, the performance of stable pools has improved dramatically, making them a viable option for quickly producing drug substance for GLP-toxicology and early-phase clinical trials in scenarios such as pandemics that demand rapid production timelines. Compared to stable CHO clones which can take several months to generate and characterize, stable pool development can be completed in only a few weeks. Here, we compared the productivity and product quality of trimeric SARS-CoV-2 spike protein ectodomains produced from stable CHO pools or clones. Using a set of biophysical and biochemical assays we show that product quality is very similar and that CHO pools demonstrate sufficient productivity to generate vaccine candidates for early clinical trials. Based on these data, we propose that regulatory guidelines should be updated to permit production of early clinical trial material from CHO pools to enable more rapid and cost-effective clinical evaluation of potentially life-saving vaccines.

Keywords: CHO clones; CHO pools; SARS-CoV-2 spike protein; product comparability; quality attributes.

PubMed Disclaimer

References

REFERENCES

    1. Agostinetto, R., Rossi, M., Dawson, J., Lim, A., Simoneau, M. H., Boucher, C., Valldorf, B., Ross-Gillespie, A., Jardine, J. G., Sok, D., Burton, D. R., Hassell, T., Broly, H., Palinsky, W., Dupraz, P., Feinberg, M., & Dey, A. K. (2022). Rapid cGMP manufacturing of COVID-19 monoclonal antibody using stable CHO cell pools. Biotechnology and Bioengineering, 119(2), 663-666. https://doi.org/10.1002/bit.27995
    1. Akache, B., Renner, T. M., Stuible, M., Rohani, N., Cepero-Donates, Y., Deschatelets, L., & Hill, J. J. (2022). Immunogenicity of SARS-CoV-2 spike antigens derived from Beta & Delta variants of concern. NPJ Vaccines, 7(1), 1-7.
    1. Akache, B., Renner, T. M., Tran, A., Deschatelets, L., Dudani, R., Harrison, B. A., Duque, D., Haukenfrers, J., Rossotti, M. A., Gaudreault, F., Hemraz, U. D., Lam, E., Régnier, S., Chen, W., Gervais, C., Stuible, M., Krishnan, L., Durocher, Y., & McCluskie, M. J. (2021). Immunogenic and efficacious SARS-CoV-2 vaccine based on resistin-trimerized spike antigen SmT1 and SLA archaeosome adjuvant. Scientific Reports, 11(1), 21849.
    1. Balasubramanian, S., Matasci, M., Kadlecova, Z., Baldi, L., Hacker, D. L., & Wurm, F. M. (2015). Rapid recombinant protein production from piggyBac transposon-mediated stable CHO cell pools. Journal of Biotechnology, 200, 61-69. https://doi.org/10.1016/j.jbiotec.2015.03.001
    1. Balasubramanian, S., Peery, R. B., Minshull, J., Lee, M., White, R., Kelly, R. M., & Barnard, G. C. (2018). Generation of high expressing Chinese hamster ovary cell pools using the Leap-In transposon system. Biotechnology Journal, 13(10), 1700748.

Publication types

LinkOut - more resources