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McIlwain DR, Chen H, Rahil Z, et al. Human influenza virus challenge identifies cellular correlates of protection for oral vaccination. Cell Host Microbe. 2021;29(12):1828-1837.e5doi: 10.1016/j.chom.2021.10.009.
McIlwain, D. R., Chen, H., Rahil, Z., Bidoki, N. H., Jiang, S., Bjornson, Z., Kolhatkar, N. S., Martinez, C. J., Gaudillière, B., Hedou, J., Mukherjee, N., Schürch, C. M., Trejo, A., Affrime, M., Bock, B., Kim, K., Liebowitz, D., Aghaeepour, N., Tucker, S. N., & Nolan, G. P. (2021). Human influenza virus challenge identifies cellular correlates of protection for oral vaccination. Cell host & microbe, 29(12), 1828-1837.e5. https://doi.org/10.1016/j.chom.2021.10.009
McIlwain, David R, et al. "Human influenza virus challenge identifies cellular correlates of protection for oral vaccination." Cell host & microbe vol. 29,12 (2021): 1828-1837.e5. doi: https://doi.org/10.1016/j.chom.2021.10.009
McIlwain DR, Chen H, Rahil Z, Bidoki NH, Jiang S, Bjornson Z, Kolhatkar NS, Martinez CJ, Gaudillière B, Hedou J, Mukherjee N, Schürch CM, Trejo A, Affrime M, Bock B, Kim K, Liebowitz D, Aghaeepour N, Tucker SN, Nolan GP. Human influenza virus challenge identifies cellular correlates of protection for oral vaccination. Cell Host Microbe. 2021 Dec 08;29(12):1828-1837.e5. doi: 10.1016/j.chom.2021.10.009. Epub 2021 Nov 15. PMID: 34784508; PMCID: PMC8665113.
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Cell Host Microbe. 2021 Dec 08;29(12):1828-1837.e5. doi: 10.1016/j.chom.2021.10.009. Epub 2021 Nov 15.

Human influenza virus challenge identifies cellular correlates of protection for oral vaccination.

Cell host & microbe

David R McIlwain, Han Chen, Zainab Rahil, Neda Hajiakhoond Bidoki, Sizun Jiang, Zach Bjornson, Nikita S Kolhatkar, C Josefina Martinez, Brice Gaudillière, Julien Hedou, Nilanjan Mukherjee, Christian M Schürch, Angelica Trejo, Melton Affrime, Bonnie Bock, Kenneth Kim, David Liebowitz, Nima Aghaeepour, Sean N Tucker, Garry P Nolan

Affiliations

  1. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA; WCCT Global, Cypress, CA, USA. Electronic address: [email protected].
  2. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  3. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Biomedical Informatics, Stanford University School of Medicine, Stanford, CA, USA.
  4. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  5. Vaxart, Inc., South San Francisco, CA, USA.
  6. Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  7. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA; Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany.
  8. WCCT Global, Cypress, CA, USA.
  9. Ark Clinical Research, LLC, Long Beach, CA, USA.
  10. Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Biomedical Informatics, Stanford University School of Medicine, Stanford, CA, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  11. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.

PMID: 34784508 PMCID: PMC8665113 DOI: 10.1016/j.chom.2021.10.009

Abstract

Developing new influenza vaccines with improved performance and easier administration routes hinges on defining correlates of protection. Vaccine-elicited cellular correlates of protection for influenza in humans have not yet been demonstrated. A phase-2 double-blind randomized placebo and active (inactivated influenza vaccine) controlled study provides evidence that a human-adenovirus-5-based oral influenza vaccine tablet (VXA-A1.1) can protect from H1N1 virus challenge in humans. Mass cytometry characterization of vaccine-elicited cellular immune responses identified shared and vaccine-type-specific responses across B and T cells. For VXA-A1.1, the abundance of hemagglutinin-specific plasmablasts and plasmablasts positive for integrin α4β7, phosphorylated STAT5, or lacking expression of CD62L at day 8 were significantly correlated with protection from developing viral shedding following virus challenge at day 90 and contributed to an effective machine learning model of protection. These findings reveal the characteristics of vaccine-elicited cellular correlates of protection for an oral influenza vaccine.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: CyTOF; cellular immunity; correlates of protection; influenza challenge study; influenza vaccine; mass cytometry

Conflict of interest statement

Declaration of interests The authors declare the following competing interests: S.N.T., D.L., N.S.K., and C.J.M. are current or former employees of Vaxart Inc. G.P.N. and D.R.M. have received research

References

  1. Blood. 2013 Dec 5;122(24):3940-50 - PubMed
  2. Sci Immunol. 2017 Feb;2(8): - PubMed
  3. Sci Transl Med. 2013 Mar 13;5(176):176ra32 - PubMed
  4. Sci Rep. 2016 Nov 24;6:37295 - PubMed
  5. Immunol Rev. 2016 Mar;270(1):65-77 - PubMed
  6. Curr Opin Immunol. 2019 Aug;59:9-14 - PubMed
  7. Nat Protoc. 2015 Feb;10(2):316-33 - PubMed
  8. Cell. 2020 Nov 25;183(5):1383-1401.e19 - PubMed
  9. Immunol Rev. 2005 Aug;206:32-63 - PubMed
  10. PLoS Pathog. 2013 Mar;9(3):e1003207 - PubMed
  11. Lancet Infect Dis. 2015 Sep;15(9):1041-1048 - PubMed
  12. Hum Vaccin Immunother. 2019;15(5):1021-1030 - PubMed
  13. Nat Commun. 2020 Jul 27;11(1):3738 - PubMed
  14. PLoS One. 2016 Jan 05;11(1):e0146010 - PubMed
  15. FASEB J. 2018 Jan;32(1):5-15 - PubMed
  16. J Immunol. 2008 Apr 1;180(7):4805-15 - PubMed
  17. Immunohorizons. 2020 Dec 11;4(12):774-788 - PubMed
  18. Expert Rev Vaccines. 2018 Nov;17(11):977-987 - PubMed
  19. Oncogene. 2007 Jan 11;26(2):224-33 - PubMed
  20. J Virol. 2014 Apr;88(8):4047-57 - PubMed
  21. Vaccine. 2020 Feb 24;38(9):2250-2257 - PubMed
  22. Vaccine. 2017 Jun 8;35(26):3355-3363 - PubMed
  23. Front Immunol. 2012 Apr 17;3:78 - PubMed
  24. Nat Med. 2012 Jan 29;18(2):274-80 - PubMed
  25. Nat Med. 2005 Apr;11(4 Suppl):S45-53 - PubMed
  26. Cells. 2020 Dec 08;9(12): - PubMed
  27. Nat Immunol. 2005 Mar;6(3):303-13 - PubMed
  28. Nat Biotechnol. 2018 Dec 03;: - PubMed
  29. BMC Bioinformatics. 2011 Mar 17;12:77 - PubMed
  30. Blood. 2020 Jan 2;135(1):7-16 - PubMed
  31. Cytometry A. 2013 May;83(5):483-94 - PubMed
  32. Front Cell Infect Microbiol. 2019 Apr 17;9:107 - PubMed
  33. Nat Immunol. 2019 May;20(5):613-625 - PubMed
  34. Front Immunol. 2014 Aug 20;5:374 - PubMed
  35. Int J Infect Dis. 2016 Aug;49:18-29 - PubMed
  36. Cell Rep. 2020 Apr 28;31(4):107569 - PubMed
  37. Virol J. 2015 Feb 03;12:13 - PubMed
  38. PLoS One. 2020 Nov 12;15(11):e0242211 - PubMed
  39. Clin Vaccine Immunol. 2010 Jul;17(7):1055-65 - PubMed
  40. JCI Insight. 2020 May 21;5(10): - PubMed
  41. J Transl Med. 2018 Jun 5;16(1):153 - PubMed
  42. J Immunol. 2014 Oct 1;193(7):3528-37 - PubMed
  43. J Clin Invest. 2020 Nov 2;130(11):5800-5816 - PubMed
  44. Lancet Infect Dis. 2020 Apr;20(4):435-444 - PubMed

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