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Frontiers in immunology
2023;14 1246826.

Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primates.

Andrew D White, Andy C Tran, Laura Sibley, Charlotte Sarfas, Alexandra L Morrison, Steve Lawrence, Mike Dennis, Simon Clark, Sirine Zadi, Faye Lanni, Emma Rayner, Alastair Copland, Peter Hart, Gil Reynolds Diogo, Matthew J Paul, Miyoung Kim, Fergus Gleeson, Francisco J Salguero, Mahavir Singh, Matthias Stehr, Simon M Cutting, Juan I Basile, Martin E Rottenberg, Ann Williams, Sally A Sharpe, Rajko Reljic
Author Information
  1. Andrew D White: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  2. Andy C Tran: Institute for Infection and Immunity, St George's University of London, London, United Kingdom.
  3. Laura Sibley: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  4. Charlotte Sarfas: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  5. Alexandra L Morrison: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  6. Steve Lawrence: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  7. Mike Dennis: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  8. Simon Clark: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  9. Sirine Zadi: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  10. Faye Lanni: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  11. Emma Rayner: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  12. Alastair Copland: Institute for Infection and Immunity, St George's University of London, London, United Kingdom.
  13. Peter Hart: Institute for Infection and Immunity, St George's University of London, London, United Kingdom.
  14. Gil Reynolds Diogo: Institute for Infection and Immunity, St George's University of London, London, United Kingdom.
  15. Matthew J Paul: Institute for Infection and Immunity, St George's University of London, London, United Kingdom.
  16. Miyoung Kim: Institute for Infection and Immunity, St George's University of London, London, United Kingdom.
  17. Fergus Gleeson: Department of Oncology, The Churchill Hospital, Oxford, United Kingdom.
  18. Francisco J Salguero: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  19. Mahavir Singh: Lionex GmbH, Braunschweig, Germany.
  20. Matthias Stehr: Lionex GmbH, Braunschweig, Germany.
  21. Simon M Cutting: School of Biological Sciences, Royal Holloway University of London, Surrey, United Kingdom.
  22. Juan I Basile: Department of Microbiology, Tumour and Cell Biology and Centre for Tuberculosis Research, Karolinska Institute, Stockholm, Sweden.
  23. Martin E Rottenberg: Department of Microbiology, Tumour and Cell Biology and Centre for Tuberculosis Research, Karolinska Institute, Stockholm, Sweden.
  24. Ann Williams: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  25. Sally A Sharpe: United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, United Kingdom.
  26. Rajko Reljic: Institute for Infection and Immunity, St George's University of London, London, United Kingdom.
PMID: 37881438 DOI: 10.3389/fimmu.2023.1246826

Abstract

Tuberculosis remains a major health threat globally and a more effective vaccine than the current Bacillus Calmette Guerin (BCG) is required, either to replace or boost it. The Spore-FP1 mucosal vaccine candidate is based on the fusion protein of Ag85B-Acr-HBHA/heparin-binding domain, adsorbed on the surface of inactivated spores. The candidate conferred significant protection against challenge in naïve guinea pigs and markedly improved protection in the lungs and spleens of animals primed with BCG. We then immunized rhesus macaques with BCG intradermally, and subsequently boosted with one intradermal and one aerosol dose of Spore-FP1, prior to challenge with low dose aerosolized Erdman strain. Following vaccination, animals did not show any adverse reactions and displayed higher antigen specific cellular and antibody immune responses compared to BCG alone but this did not translate into significant improvement in disease pathology or bacterial burden in the organs.

Keywords

aerosol vaccine lungs non-human primates tuberculosis vaccine

References

  1. Lancet. 2013 Mar 23;381(9871):1021-8 [PMID: 23391465]
  2. J Immunol. 2011 Mar 1;186(5):3113-9 [PMID: 21257971]
  3. Clin Exp Immunol. 2006 Mar;143(3):467-73 [PMID: 16487246]
  4. Infect Immun. 2004 Nov;72(11):6622-32 [PMID: 15501795]
  5. Vaccine. 2010 Jan 22;28(4):1106-16 [PMID: 19853680]
  6. Am Rev Respir Dis. 1973 Mar;107(3):351-8 [PMID: 4632221]
  7. Clin Vaccine Immunol. 2010 Aug;17(8):1170-82 [PMID: 20534795]
  8. Vaccine. 2015 Nov 27;33(48):6800-8 [PMID: 26478198]
  9. J Comp Pathol. 2015 Feb-Apr;152(2-3):217-26 [PMID: 25481611]
  10. J Immunol. 2014 Aug 15;193(4):1799-811 [PMID: 25024382]
  11. J Appl Microbiol. 2011 Aug;111(2):350-9 [PMID: 21651681]
  12. Infect Immun. 2005 Jun;73(6):3814-6 [PMID: 15908420]
  13. Vaccine. 2015 May 28;33(23):2710-8 [PMID: 25869896]
  14. Tuberculosis (Edinb). 2005 Jan-Mar;85(1-2):29-38 [PMID: 15687025]
  15. Clin Vaccine Immunol. 2015 Sep;22(9):992-1003 [PMID: 26108288]
  16. J Pharmacol Toxicol Methods. 2004 Jan-Feb;49(1):39-55 [PMID: 14670693]
  17. NPJ Vaccines. 2020 May 14;5(1):39 [PMID: 32435513]
  18. Int J Infect Dis. 2017 Mar;56:268-273 [PMID: 28163168]
  19. Tuberculosis (Edinb). 2016 Jan;96:1-12 [PMID: 26786648]
  20. Lab Anim. 2018 Dec;52(6):599-610 [PMID: 29482429]
  21. NPJ Vaccines. 2019 May 28;4:21 [PMID: 31149352]
  22. Nat Med. 2018 Feb;24(2):130-143 [PMID: 29334373]
  23. Vaccine. 2013 Feb 18;31(9):1340-8 [PMID: 23290835]
  24. Front Immunol. 2020 Oct 20;11:582833 [PMID: 33193394]
  25. Nature. 2001 Jul 12;412(6843):190-4 [PMID: 11449276]
  26. Tuberculosis (Edinb). 2007 Mar;87(2):94-101 [PMID: 16815096]
  27. Infect Immun. 2013 Nov;81(11):4071-80 [PMID: 23959722]
  28. Lancet Respir Med. 2018 Apr;6(4):287-298 [PMID: 29595510]
  29. PLoS Med. 2019 Apr 30;16(4):e1002790 [PMID: 31039172]
  30. Tuberculosis (Edinb). 2016 Dec;101:174-190 [PMID: 27865390]
  31. Nature. 2020 Jan;577(7788):95-102 [PMID: 31894150]
  32. Nat Commun. 2015 Oct 13;6:8533 [PMID: 26460802]
  33. Tuberculosis (Edinb). 2016 Jan;96:141-9 [PMID: 26723465]
  34. J Hyg (Lond). 1969 Sep;67(3):437-48 [PMID: 5258223]
  35. Pharmaceutics. 2020 Apr 25;12(5): [PMID: 32344890]
  36. Front Immunol. 2018 Mar 12;9:346 [PMID: 29593708]
  37. N Engl J Med. 2019 Dec 19;381(25):2429-2439 [PMID: 31661198]
  38. J Immunol. 2015 Aug 1;195(3):1015-24 [PMID: 26123354]
  39. N Engl J Med. 2018 Jul 12;379(2):138-149 [PMID: 29996082]
  40. Nat Med. 2019 Feb;25(2):255-262 [PMID: 30664782]
  41. Front Immunol. 2020 Feb 27;11:316 [PMID: 32174919]
  42. Nat Commun. 2021 Nov 22;12(1):6774 [PMID: 34811370]
  43. Cancer Res. 2001 May 15;61(10):4055-60 [PMID: 11358825]
  44. PLoS One. 2009 Jun 10;4(6):e5856 [PMID: 19516906]
  45. FEMS Microbiol Lett. 2014 Sep;358(2):170-9 [PMID: 24990572]
  46. NPJ Vaccines. 2021 Jan 4;6(1):4 [PMID: 33397991]
  47. Immunology. 2004 Mar;111(3):328-33 [PMID: 15009434]
  48. Clin Vaccine Immunol. 2013 May;20(5):663-72 [PMID: 23446219]

MeSH Term

Guinea Pigs
Animals
Tuberculosis Vaccines
BCG Vaccine
Macaca mulatta
Antigens, Bacterial
Tuberculosis
Mycobacterium bovis
Mycobacterium tuberculosis
Spores

Chemicals

Tuberculosis Vaccines
BCG Vaccine
Antigens, Bacterial
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 2

Word Cloud

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