Stark Jessica C, Jaroentomeechai Thapakorn, Moeller Tyler D, Hershewe Jasmine M, Warfel Katherine F, Moricz Bridget S, Martini Anthony M, Dubner Rachel S, Hsu Karen J, Stevenson Taylor C, Jones Bradley D, DeLisa Matthew P, Jewett Michael C
Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA.
Center for Synthetic Biology, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA.
Sci Adv. 2021 Feb 3;7(6). doi: 10.1126/sciadv.abe9444. Print 2021 Feb.
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 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 subsp. (type A) strain Schu S4 protected mice from lethal intranasal challenge. The iVAX platform promises to accelerate development of new conjugate vaccines with increased access through refrigeration-independent distribution and portable production.
结合疫苗是预防细菌感染最有效的方法之一。然而,由于集中生产和冷链配送要求,现有的生产方法限制了结合疫苗的可及性。为解决这些限制,我们开发了一种模块化技术,用于在来自解毒的、无致病性的冻干裂解物中进行体外结合疫苗表达(iVAX)。复水后,iVAX反应在1小时内合成针对多种细菌病原体的临床相关剂量的结合疫苗。我们表明,iVAX合成的针对土拉热弗朗西斯菌亚种(A型)菌株Schu S4的疫苗可保护小鼠免受致命的鼻内攻击。iVAX平台有望通过无需冷藏的配送和便携式生产加快新结合疫苗的开发,并提高其可及性。