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06 08, 2022;7 (11):

Bacillus Calmette-Guérin-induced trained immunity protects against SARS-CoV-2 challenge in K18-hACE2 mice.

Bao-Zhong Zhang, Huiping Shuai, Hua-Rui Gong, Jing-Chu Hu, Bingpeng Yan, Terrence Tsz-Tai Yuen, Ye-Fan Hu, Chaemin Yoon, Xiao-Lei Wang, Yuxin Hou, Xuansheng Lin, Xiner Huang, Renhao Li, Yee Man Au-Yeung, Wenjun Li, Bingjie Hu, Yue Chai, Ming Yue, Jian-Piao Cai, Guang Sheng Ling, Ivan Fan-Ngai Hung, Kwok-Yung Yuen, Jasper Fuk-Woo Chan, Jian-Dong Huang, Hin Chu
Author Information
  1. Bao-Zhong Zhang: CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  2. Huiping Shuai: State Key Laboratory of Emerging Infectious Diseases, and.
  3. Hua-Rui Gong: School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  4. Jing-Chu Hu: CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  5. Bingpeng Yan: State Key Laboratory of Emerging Infectious Diseases, and.
  6. Terrence Tsz-Tai Yuen: State Key Laboratory of Emerging Infectious Diseases, and.
  7. Ye-Fan Hu: School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  8. Chaemin Yoon: State Key Laboratory of Emerging Infectious Diseases, and.
  9. Xiao-Lei Wang: School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  10. Yuxin Hou: State Key Laboratory of Emerging Infectious Diseases, and.
  11. Xuansheng Lin: School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  12. Xiner Huang: State Key Laboratory of Emerging Infectious Diseases, and.
  13. Renhao Li: School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  14. Yee Man Au-Yeung: School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  15. Wenjun Li: CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  16. Bingjie Hu: State Key Laboratory of Emerging Infectious Diseases, and.
  17. Yue Chai: State Key Laboratory of Emerging Infectious Diseases, and.
  18. Ming Yue: School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  19. Jian-Piao Cai: State Key Laboratory of Emerging Infectious Diseases, and.
  20. Guang Sheng Ling: School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  21. Ivan Fan-Ngai Hung: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  22. Kwok-Yung Yuen: State Key Laboratory of Emerging Infectious Diseases, and.
  23. Jasper Fuk-Woo Chan: State Key Laboratory of Emerging Infectious Diseases, and.
  24. Jian-Dong Huang: CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  25. Hin Chu: State Key Laboratory of Emerging Infectious Diseases, and.
PMID: 35446790 DOI: 10.1172/jci.insight.157393

Abstract

SARS-CoV-2 has been confirmed in over 450 million confirmed cases since 2019. Although several vaccines have been certified by the WHO and people are being vaccinated on a global scale, it has been reported that multiple SARS-CoV-2 variants can escape neutralization by antibodies, resulting in vaccine breakthrough infections. Bacillus Calmette-Guérin (BCG) is known to induce heterologous protection based on trained immune responses. Here, we investigated whether BCG-induced trained immunity protected against SARS-CoV-2 in the K18-hACE2 mouse model. Our data demonstrate that i.v. BCG (BCG-i.v.) vaccination induces robust trained innate immune responses and provides protection against WT SARS-CoV-2, as well as the B.1.617.1 and B.1.617.2 variants. Further studies suggest that myeloid cell differentiation and activation of the glycolysis pathway are associated with BCG-induced training immunity in K18-hACE2 mice. Overall, our study provides the experimental evidence that establishes a causal relationship between BCG-i.v. vaccination and protection against SARS-CoV-2 challenge.

Keywords

COVID-19 Infectious disease Innate immunity

References

  1. Int J Mol Sci. 2019 Nov 26;20(23): [PMID: 31779252]
  2. Nature. 2022 Apr;604(7906):553-556 [PMID: 35240676]
  3. EBioMedicine. 2021 Nov;73:103643 [PMID: 34689086]
  4. Acta Med Indones. 2011 Jul;43(3):185-90 [PMID: 21979284]
  5. Int Rev Immunol. 2020;39(3):83-96 [PMID: 31933415]
  6. Science. 2016 Apr 22;352(6284):aaf1098 [PMID: 27102489]
  7. Lancet. 2020 Feb 15;395(10223):514-523 [PMID: 31986261]
  8. J Clin Invest. 2020 May 1;130(5):2620-2629 [PMID: 32217835]
  9. Nihon Ronen Igakkai Zasshi. 2005 Jan;42(1):34-6 [PMID: 15732353]
  10. Cell. 2020 May 28;181(5):969-977 [PMID: 32437659]
  11. Cell Mol Gastroenterol Hepatol. 2021;11(3):771-781 [PMID: 33010495]
  12. Nat Methods. 2015 Jun;12(6):523-6 [PMID: 25938372]
  13. Cell Metab. 2019 Sep 3;30(3):539-555.e11 [PMID: 31257153]
  14. Cell Rep. 2016 Dec 6;17(10):2562-2571 [PMID: 27926861]
  15. Innovation (Camb). 2021 Jul 01;2(3):100141 [PMID: 34557778]
  16. Nat Commun. 2021 Jan 8;12(1):134 [PMID: 33420022]
  17. Vaccine. 2005 Jan 26;23(10):1251-7 [PMID: 15652667]
  18. Vaccine. 2003 Jun 20;21(21-22):2782-90 [PMID: 12798618]
  19. Commun Biol. 2021 Oct 13;4(1):1196 [PMID: 34645933]
  20. Nat Rev Microbiol. 2021 Jul;19(7):409-424 [PMID: 34075212]
  21. Clin Microbiol Infect. 2019 Dec;25(12):1459-1467 [PMID: 31449870]
  22. Cell Host Microbe. 2018 Jan 10;23(1):89-100.e5 [PMID: 29324233]
  23. J Clin Invest. 2021 Jan 19;131(2): [PMID: 33211672]
  24. N Engl J Med. 2021 Jun 10;384(23):2212-2218 [PMID: 33882219]
  25. Nat Rev Urol. 2021 Oct;18(10):611-622 [PMID: 34131332]
  26. Genome Biol. 2014;15(12):550 [PMID: 25516281]
  27. N Engl J Med. 2021 Jul 8;385(2):e7 [PMID: 34077641]
  28. Cell. 2018 Jan 11;172(1-2):135-146.e9 [PMID: 29328908]
  29. Proc Natl Acad Sci U S A. 2021 May 25;118(21): [PMID: 34006644]
  30. J Clin Virol. 2021 Sep;142:104912 [PMID: 34298379]
  31. Analyst. 2017 Jan 26;142(3):442-448 [PMID: 28091625]
  32. Nat Rev Genet. 2021 Dec;22(12):757-773 [PMID: 34535792]
  33. J Leukoc Biol. 2003 Aug;74(2):277-86 [PMID: 12885945]
  34. N Engl J Med. 2020 Sep 10;383(11):1078-1080 [PMID: 32905684]
  35. Nucleic Acids Res. 2021 Jul 2;49(W1):W388-W396 [PMID: 34019663]
  36. Ann Intern Med. 2021 Dec;174(12):1770-1772 [PMID: 34662153]
  37. Viruses. 2019 Jan 16;11(1): [PMID: 30654597]
  38. Arch Dis Child. 2010 Sep;95(9):661 [PMID: 20656728]
  39. J Clin Invest. 2021 Jun 1;131(11): [PMID: 34060492]
  40. Emerg Microbes Infect. 2021 Dec;10(1):874-884 [PMID: 33890550]
  41. Nucleic Acids Res. 2020 Jan 8;48(D1):D498-D503 [PMID: 31691815]
  42. Lancet Microbe. 2021 Oct;2(10):e527-e535 [PMID: 34258603]
  43. Sci Adv. 2020 Aug 05;6(32):eabc1463 [PMID: 32923613]
  44. Nat Med. 2020 Oct;26(10):1623-1635 [PMID: 32807934]
  45. N Engl J Med. 2018 Jul 12;379(2):138-149 [PMID: 29996082]
  46. J Infect Dis. 1977 Aug;136(2):171-5 [PMID: 894076]
  47. Cell. 2018 Jan 11;172(1-2):176-190.e19 [PMID: 29328912]
  48. J Infect Dis. 2011 Jul 15;204(2):245-52 [PMID: 21673035]
  49. Sci Adv. 2021 Jun 16;7(25): [PMID: 34134991]
  50. Nature. 2010 Jun 10;465(7299):793-7 [PMID: 20535209]
  51. Allergy. 2020 Jul;75(7):1815-1819 [PMID: 32339299]
  52. Nat Metab. 2020 Feb;2(2):127-129 [PMID: 32694689]
  53. Nature. 2020 Oct;586(7830):516-527 [PMID: 32967006]
  54. Cell. 2021 Apr 29;184(9):2523 [PMID: 33930298]
  55. PLoS Pathog. 2020 Oct 29;16(10):e1008969 [PMID: 33119725]
  56. Nat Rev Immunol. 2020 Jun;20(6):335-337 [PMID: 32393823]
  57. EBioMedicine. 2021 Aug;70:103505 [PMID: 34332295]
  58. Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17537-42 [PMID: 22988082]
  59. Nature. 2022 Feb;602(7898):676-681 [PMID: 35016198]
  60. Nat Methods. 2017 Apr;14(4):417-419 [PMID: 28263959]
  61. Plant Physiol. 2006 Nov;142(3):1087-101 [PMID: 16998089]
  62. Ter Arkh. 2020 Dec 15;92(12):195-200 [PMID: 33720594]
  63. Nat Rev Drug Discov. 2019 Jul;18(7):553-566 [PMID: 30967658]
  64. Genome Biol. 2017 Nov 15;18(1):220 [PMID: 29141660]
  65. J Exp Med. 2022 Feb 7;219(2): [PMID: 34889942]
  66. J Clin Invest. 2021 Jan 19;131(2): [PMID: 33306484]
  67. Nature. 2022 Mar;603(7902):693-699 [PMID: 35062016]
  68. Lancet Microbe. 2020 May;1(1):e14-e23 [PMID: 32835326]

MeSH Term

Animals
BCG Vaccine
COVID-19
Humans
Melphalan
Mice
SARS-CoV-2
gamma-Globulins

Chemicals

BCG Vaccine
K-18 conjugate
gamma-Globulins
Melphalan
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 69

Word Cloud

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