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
Author Information
  1. Jessica C Stark: Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA. ORCID
  2. Thapakorn Jaroentomeechai: Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, 120 Olin Hall, Ithaca, NY 14853, USA. ORCID
  3. Tyler D Moeller: Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, 120 Olin Hall, Ithaca, NY 14853, USA. ORCID
  4. Jasmine M Hershewe: Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA. ORCID
  5. Katherine F Warfel: Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA. ORCID
  6. Bridget S Moricz: Department of Microbiology and Immunology, University of Iowa, 51 Newton Rd 3-403 Bowen Science Building, Iowa City, IA 52242, USA.
  7. Anthony M Martini: Department of Microbiology and Immunology, University of Iowa, 51 Newton Rd 3-403 Bowen Science Building, Iowa City, IA 52242, USA. ORCID
  8. Rachel S Dubner: Department of Biological Sciences, Northwestern University, 2205 Tech Drive Hogan Hall 2144, Evanston, IL 60208-3500, USA. ORCID
  9. Karen J Hsu: Department of Mechanical Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute B224, Evanston, IL 60208-3120, USA.
  10. Taylor C Stevenson: Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Weill Hall, Ithaca, NY 14853, USA.
  11. Bradley D Jones: Department of Microbiology and Immunology, University of Iowa, 51 Newton Rd 3-403 Bowen Science Building, Iowa City, IA 52242, USA. ORCID
  12. Matthew P DeLisa: 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. ORCID
  13. Michael C Jewett: 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. ORCID

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 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.

References

  1. Nat Biotechnol. 2018 Oct 01;: [PMID: 30272677]
  2. Lancet. 2017 Dec 2;390(10111):2472-2480 [PMID: 28965718]
  3. Sci Rep. 2015 Oct 20;5:15237 [PMID: 26482295]
  4. Vaccine. 2008 Aug 18;26(35):4434-45 [PMID: 18617296]
  5. Cell Mol Life Sci. 2008 Oct;65(20):3231-40 [PMID: 18668203]
  6. Vaccine. 2002 Oct 4;20(29-30):3465-71 [PMID: 12297391]
  7. Biochemistry. 2007 May 8;46(18):5579-85 [PMID: 17439157]
  8. Carbohydr Res. 2003 Nov 14;338(23):2539-47 [PMID: 14670715]
  9. Pediatr Infect Dis J. 2009 Oct;28(10):e276-82 [PMID: 20118683]
  10. J Immunol Res. 2018 Nov 29;2018:8087916 [PMID: 30622981]
  11. Open Biol. 2013 May 22;3(5):130002 [PMID: 23697804]
  12. Clin Microbiol Rev. 2005 Jul;18(3):465-83 [PMID: 16020685]
  13. ACS Synth Biol. 2014 Jun 20;3(6):398-409 [PMID: 24328168]
  14. Nat Rev Genet. 2020 Mar;21(3):151-170 [PMID: 31780816]
  15. Vaccine. 2017 Jun 16;35(28):3598-3606 [PMID: 28408122]
  16. Appl Environ Microbiol. 2011 Feb;77(3):871-81 [PMID: 21131519]
  17. Cold Spring Harb Perspect Biol. 2016 Dec 1;8(12): [PMID: 27742731]
  18. Vaccine. 2000 Nov 22;19(7-8):716-25 [PMID: 11115692]
  19. Curr Opin Biotechnol. 2006 Aug;17(4):341-6 [PMID: 16828275]
  20. Bull World Health Organ. 2011 May 1;89(5):324-5 [PMID: 21556298]
  21. Nat Biotechnol. 2017 Jul;35(7):672-675 [PMID: 28553942]
  22. Infect Immun. 2007 Mar;75(3):1359-63 [PMID: 17220311]
  23. Vaccine. 2002 Oct 4;20(29-30):3509-22 [PMID: 12297396]
  24. PLoS One. 2014 Aug 19;9(8):e105215 [PMID: 25137044]
  25. Infect Immun. 1989 Mar;57(3):937-43 [PMID: 2645215]
  26. Vaccine. 2015 Aug 26;33(36):4594-601 [PMID: 26162850]
  27. EMBO J. 2006 May 3;25(9):1957-66 [PMID: 16619027]
  28. Biotechnol Bioeng. 2001 Aug 20;74(4):309-16 [PMID: 11410855]
  29. FEBS Lett. 2010 May 3;584(9):1721-7 [PMID: 19836392]
  30. Pediatr Infect Dis J. 2009 Apr;28(4 Suppl):S97-S108 [PMID: 19325452]
  31. Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1464-9 [PMID: 23297218]
  32. Nat Chem Biol. 2014 Oct;10(10):816-22 [PMID: 25129029]
  33. Hum Vaccin. 2007 Sep-Oct;3(5):176-82 [PMID: 17786035]
  34. Infect Immun. 2002 Sep;70(9):4946-54 [PMID: 12183540]
  35. Biotechnol J. 2016 Feb;11(2):274-81 [PMID: 26380966]
  36. Infect Immun. 1998 May;66(5):2093-8 [PMID: 9573094]
  37. Nat Biomed Eng. 2018 Sep;2(9):675-686 [PMID: 31015674]
  38. Hum Vaccin Immunother. 2014;10(9):2744-53 [PMID: 25483488]
  39. Biotechnol J. 2015 Jan;10(1):199-209 [PMID: 25263089]
  40. Biotechnol Bioeng. 2018 Mar;115(3):739-750 [PMID: 29178580]
  41. Expert Rev Anti Infect Ther. 2015 Feb;13(2):141-4 [PMID: 25413334]
  42. N Engl J Med. 2006 Oct 19;355(16):1699-713 [PMID: 17050894]
  43. Infect Immun. 1998 Dec;66(12):5848-53 [PMID: 9826364]
  44. Clin Microbiol Rev. 1991 Jan;4(1):80-128 [PMID: 1672263]
  45. Lancet Infect Dis. 2012 Oct;12(10):757-64 [PMID: 22818241]
  46. Carbohydr Res. 1987 Jul 15;165(1):87-92 [PMID: 2444338]
  47. Lancet Glob Health. 2018 Jul;6(7):e744-e757 [PMID: 29903376]
  48. Lancet. 2013 Jan 19;381(9862):214-22 [PMID: 23158882]
  49. Vaccine. 2001 Aug 14;19(31):4465-72 [PMID: 11483272]
  50. Front Microbiol. 2014 Jul 29;5:381 [PMID: 25120536]
  51. J Infect Dev Ctries. 2011 Dec 13;5(12):856-62 [PMID: 22169784]
  52. Vaccine. 2009 Jan 22;27(4):597-605 [PMID: 19022323]
  53. Microb Cell Fact. 2010 Aug 11;9:61 [PMID: 20701771]
  54. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5 [PMID: 10829079]
  55. J Pharm Sci. 2011 Jan;100(1):34-7 [PMID: 20575063]
  56. Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):3016-21 [PMID: 15703289]
  57. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3099-104 [PMID: 20133740]
  58. Clin Vaccine Immunol. 2016 Dec 5;23(12):908-917 [PMID: 27581434]
  59. J Biotechnol. 2000 Jan 21;76(2-3):97-119 [PMID: 10656326]
  60. Infect Immun. 1995 Aug;63(8):3218-21 [PMID: 7622252]
  61. Carbohydr Res. 1984 Mar 15;126(2):249-59 [PMID: 6370430]
  62. Lancet Infect Dis. 2017 May;17(5):528-537 [PMID: 28238601]
  63. J Infect Dis. 2014 May 15;209(10):1551-61 [PMID: 24308931]
  64. Immunology. 2012 Jul;136(3):352-60 [PMID: 22486311]
  65. Vaccine. 2017 Apr 19;35(17):2217-2223 [PMID: 27670076]
  66. Bull World Health Organ. 2014 Feb 1;92(2):86-92 [PMID: 24623901]
  67. J Med Microbiol. 2003 Oct;52(Pt 10):845-851 [PMID: 12972577]
  68. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):E3609-18 [PMID: 27274048]
  69. Glycoconj J. 2013 Jul;30(5):511-22 [PMID: 23053636]
  70. Biotechnol Bioeng. 2004 Apr 5;86(1):19-26 [PMID: 15007837]
  71. Cell. 2016 Sep 22;167(1):248-259.e12 [PMID: 27662092]
  72. Nat Commun. 2016 Jul 29;7:12211 [PMID: 27470089]
  73. Vaccine. 2009 Oct 30;27(46):6468-70 [PMID: 19555714]
  74. J Dev Areas. 1988 Apr;22(3):321-32 [PMID: 12342353]
  75. Nat Rev Microbiol. 2004 Dec;2(12):967-78 [PMID: 15550942]
  76. Vaccine. 2004 Jun 2;22(17-18):2209-20 [PMID: 15149779]
  77. Microsyst Nanoeng. 2019 Mar 25;5:13 [PMID: 31057940]
  78. Infect Immun. 2004 Sep;72(9):5383-91 [PMID: 15322036]
  79. J Biotechnol. 2011 Dec 20;156(4):245-52 [PMID: 21889551]
  80. N Engl J Med. 2014 Nov 13;371(20):1889-99 [PMID: 25386897]
  81. Biotechnol Bioeng. 2004 Jan 20;85(2):122-9 [PMID: 14704994]
  82. Nat Commun. 2018 Jul 12;9(1):2686 [PMID: 30002445]
  83. JAMA. 2006 Apr 12;295(14):1668-74 [PMID: 16609088]

Grants

  1. T32 EB023860/NIBIB NIH HHS

Word Cloud

Created with Highcharts 10.0.0vaccinesconjugateiVAXbacterialaccessproductiondistributionportableConjugateamongeffectivemethodspreventinginfectionsHoweverexistingmanufacturingapproacheslimitduecentralizedcoldchainrequirementsaddresslimitationsdevelopedmodulartechnologyvitrovaccineexpressionfreeze-driedlysatesdetoxifiednonpathogenicUponrehydrationreactionssynthesizeclinicallyrelevantdosesdiversepathogens1hourshowiVAX-synthesizedsubsptypestrainSchuS4protectedmicelethalintranasalchallengeplatformpromisesacceleratedevelopmentnewincreasedrefrigeration-independentOn-demandbiomanufacturingprotective

Similar Articles

Cited By