On-demand biomanufacturing of protective conjugate vaccines

Jessica C Stark; Thapakorn Jaroentomeechai; Tyler D Moeller; Jasmine M Hershewe; Katherine F Warfel; Bridget S Moricz; Anthony M Martini; Rachel S Dubner; Karen J Hsu; Taylor C Stevenson; Bradley D Jones; Matthew P DeLisa; Michael C Jewett

doi:10.1126/sciadv.abe9444

On-demand biomanufacturing of protective conjugate vaccines

Sci Adv. 2021 Feb 3;7(6):eabe9444. doi: 10.1126/sciadv.abe9444. Print 2021 Feb.

Authors

Jessica C Stark^{1

2

3}, Thapakorn Jaroentomeechai⁴, Tyler D Moeller⁴, Jasmine M Hershewe^{1

2

3}, Katherine F Warfel^{1

2

3}, Bridget S Moricz⁵, Anthony M Martini⁵, Rachel S Dubner⁶, Karen J Hsu⁷, Taylor C Stevenson⁸, Bradley D Jones^{5

9}, Matthew P DeLisa^{10

8}, Michael C Jewett^{11

2

3

12

13}

Affiliations

¹ Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA.
² Center for Synthetic Biology, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA.
³ Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Drive, Evanston, IL 60208-3120, USA.
⁴ Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, 120 Olin Hall, Ithaca, NY 14853, USA.
⁵ Department of Microbiology and Immunology, University of Iowa, 51 Newton Rd 3-403 Bowen Science Building, Iowa City, IA 52242, USA.
⁶ Department of Biological Sciences, Northwestern University, 2205 Tech Drive Hogan Hall 2144, Evanston, IL 60208-3500, USA.
⁷ Department of Mechanical Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute B224, Evanston, IL 60208-3120, USA.
⁸ Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Weill Hall, Ithaca, NY 14853, USA.
⁹ Graduate Program in Genetics, 431 Newton Rd, University of Iowa, Iowa City, IA 52242, USA.
¹⁰ Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, 120 Olin Hall, Ithaca, NY 14853, USA. md255@cornell.edu m-jewett@northwestern.edu.
¹¹ Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA. md255@cornell.edu m-jewett@northwestern.edu.
¹² Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 676 N. St Clair St, Suite 1200, Chicago, IL 60611-3068, USA.
¹³ Simpson-Querrey Institute, Northwestern University, 303 E. Superior St, Suite 11-131 Chicago, IL 60611-2875, USA.

Abstract

Conjugate vaccines are among the most effective methods for preventing bacterial infections. However, existing manufacturing approaches limit access to conjugate vaccines due to centralized production and cold chain distribution requirements. To address these limitations, we developed a modular technology for in vitro conjugate vaccine expression (iVAX) in portable, freeze-dried lysates from detoxified, nonpathogenic Escherichia coli. Upon rehydration, iVAX reactions synthesize clinically relevant doses of conjugate vaccines against diverse bacterial pathogens in 1 hour. We show that iVAX-synthesized vaccines against Francisella tularensis subsp. tularensis (type A) strain Schu S4 protected mice from lethal intranasal F. tularensis challenge. The iVAX platform promises to accelerate development of new conjugate vaccines with increased access through refrigeration-independent distribution and portable production.

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Grants and funding

T32 EB023860/EB/NIBIB NIH HHS/United States