On-demand biomanufacturing of protective conjugate vaccines

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.
Funding Information
  • National Science Foundation (CBET 1159581)
  • National Science Foundation (CBET 1264701)
  • National Science Foundation (MCB 1413563)
  • David and Lucile Packard Foundation
  • Defense Threat Reduction Agency (HDTRA1-15-10052/P00001)
  • Camille and Henry Dreyfus Foundation (Teacher Scholar Program)