1932

Abstract

Trained immunity is defined as the de facto memory characteristics induced in innate immune cells after exposure to microbial stimuli after infections or certain types of vaccines. Through epigenetic and metabolic reprogramming of innate immune cells after exposure to these stimuli, trained immunity induces an enhanced nonspecific protection by improving the inflammatory response upon restimulation with the same or different pathogens. Recent studies have increasingly shown that trained immunity can, on the one hand, be induced by exposure to viruses; on the other hand, when induced, it can also provide protection against heterologous viral infections. In this review we explore current knowledge on trained immunity and its relevance for viral infections, as well as its possible future uses.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-virology-091919-072546
2022-09-29
2024-06-20
Loading full text...

Full text loading...

/deliver/fulltext/virology/9/1/annurev-virology-091919-072546.html?itemId=/content/journals/10.1146/annurev-virology-091919-072546&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Lester SN, Li K. 2014. Toll-like receptors in antiviral innate immunity. J. Mol. Biol. 426:1246–64
    [Crossref] [Google Scholar]
  2. 2.
    Barbalat R, Lau L, Locksley RM, Barton GM. 2009. Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands. Nat. Immunol. 10:1200–7
    [Crossref] [Google Scholar]
  3. 3.
    Murawski MR, Bowen GN, Cerny AM, Anderson LJ, Haynes LM et al. 2009. Respiratory syncytial virus activates innate immunity through Toll-like receptor 2. J. Virol. 83:1492–500
    [Crossref] [Google Scholar]
  4. 4.
    Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP et al. 2000. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat. Immunol. 1:398–401
    [Crossref] [Google Scholar]
  5. 5.
    Ekchariyawat P, Hamel R, Bernard E, Wichit S, Surasombatpattana P et al. 2015. Inflammasome signaling pathways exert antiviral effect against Chikungunya virus in human dermal fibroblasts. Infect. Genet. Evol. 32:401–8
    [Crossref] [Google Scholar]
  6. 6.
    Hamel R, Dejarnac O, Wichit S, Ekchariyawat P, Neyret A et al. 2015. Biology of Zika virus infection in human skin cells. J. Virol. 89:8880–96
    [Crossref] [Google Scholar]
  7. 7.
    Allen IC, Scull MA, Moore CB, Holl EK, McElvania-TeKippe E et al. 2009. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 30:556–65
    [Crossref] [Google Scholar]
  8. 8.
    Plotkin SA, Plotkin SA. 2008. Correlates of vaccine-induced immunity. Clin. Infect. Dis. 47:401–9
    [Crossref] [Google Scholar]
  9. 9.
    Mason RA, Tauraso NM, Spertzel RO, Ginn RK. 1973. Yellow fever vaccine: direct challenge of monkeys given graded doses of 17D vaccine. Appl. Microbiol. 25:539–44
    [Crossref] [Google Scholar]
  10. 10.
    McElhaney JE, Xie D, Hager WD, Barry MB, Wang Y et al. 2006. T cell responses are better correlates of vaccine protection in the elderly. J. Immunol. 176:6333–39
    [Crossref] [Google Scholar]
  11. 11.
    Goodridge HS, Ahmed SS, Curtis N, Kollmann TR, Levy O et al. 2016. Harnessing the beneficial heterologous effects of vaccination. Nat. Rev. Immunol. 16:392–400
    [Crossref] [Google Scholar]
  12. 12.
    Netea MG, Quintin J, van der Meer JW. 2011. Trained immunity: a memory for innate host defense. Cell Host Microbe 9:355–61
    [Crossref] [Google Scholar]
  13. 13.
    Quintin J, Cheng SC, van der Meer JW, Netea MG. 2014. Innate immune memory: towards a better understanding of host defense mechanisms. Curr. Opin. Immunol. 29:1–7
    [Crossref] [Google Scholar]
  14. 14.
    Ross AF. 1961. Systemic acquired resistance induced by localized virus infections in plants. Virology 14:340–58
    [Crossref] [Google Scholar]
  15. 15.
    Luna E, Bruce TJ, Roberts MR, Flors V, Ton J. 2012. Next-generation systemic acquired resistance. Plant Physiol. 158:844–53
    [Crossref] [Google Scholar]
  16. 16.
    Diezma-Navas L, Pérez-González A, Artaza H, Alonso L, Caro E et al. 2019. Crosstalk between epigenetic silencing and infection by tobacco rattle virus in Arabidopsis. Mol. Plant Pathol. 20:1439–52
    [Crossref] [Google Scholar]
  17. 17.
    Luna E, Ton J. 2012. The epigenetic machinery controlling transgenerational systemic acquired resistance. Plant Signal. Behav. 7:615–18
    [Crossref] [Google Scholar]
  18. 18.
    Moret Y. 2006.. “ Trans-generational immune priming”: specific enhancement of the antimicrobial immune response in the mealworm beetle, Tenebrio molitor. Proc. R. Soc. B 273:1399–405
    [Crossref] [Google Scholar]
  19. 19.
    Moret Y, Siva-Jothy MT. 2003. Adaptive innate immunity? Responsive-mode prophylaxis in the mealworm beetle, Tenebrio molitor. Proc. R. Soc. B 270:2475–80
    [Crossref] [Google Scholar]
  20. 20.
    Vargas V, Cime-Castillo J, Lanz-Mendoza H. 2020. Immune priming with inactive dengue virus during the larval stage of Aedes aegypti protects against the infection in adult mosquitoes. Sci. Rep. 10:6723
    [Crossref] [Google Scholar]
  21. 21.
    Mondotte JA, Gausson V, Frangeul L, Suzuki Y, Vazeille M et al. 2020. Evidence for long-lasting transgenerational antiviral immunity in insects. Cell Rep 33:108506
    [Crossref] [Google Scholar]
  22. 22.
    Jensen KJ, Larsen N, Biering-Sørensen S, Andersen A, Eriksen HB et al. 2015. Heterologous immunological effects of early BCG vaccination in low-birth-weight infants in Guinea-Bissau: a randomized-controlled trial. J. Infect. Dis. 211:956–67
    [Crossref] [Google Scholar]
  23. 23.
    Näslund C. 1932. Resultats des experiences de vaccination par le BCG poursuivies dans le Norrbotten (Suède) (Septembre 1927–Décembre 1931). Vaccination Preventative de Tuberculose, Rapports et Documents Paris: Institut Pasteur
    [Google Scholar]
  24. 24.
    Aaby P, Roth A, Ravn H, Napirna BM, Rodrigues A et al. 2011. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period?. J. Infect. Dis. 204:245–52
    [Crossref] [Google Scholar]
  25. 25.
    Aaby P, Gustafson P, Roth A, Rodrigues A, Fernandes M et al. 2006. Vaccinia scars associated with better survival for adults. An observational study from Guinea-Bissau. Vaccine 24:5718–25
    [Crossref] [Google Scholar]
  26. 26.
    Jensen ML, Dave S, Schim van der Loeff M, da Costa C, Vincent T et al. 2006. Vaccinia scars associated with improved survival among adults in rural Guinea-Bissau. PLOS ONE 1:e101
    [Crossref] [Google Scholar]
  27. 27.
    Aaby P, Martins CL, Garly ML, Balé C, Andersen A et al. 2010. Non-specific effects of standard measles vaccine at 4.5 and 9 months of age on childhood mortality: randomised controlled trial. BMJ 341:c6495
    [Crossref] [Google Scholar]
  28. 28.
    Veirum JE, Sodemann M, Biai S, Jakobsen M, Garly ML et al. 2005. Routine vaccinations associated with divergent effects on female and male mortality at the paediatric ward in Bissau, Guinea-Bissau. Vaccine 23:1197–204
    [Crossref] [Google Scholar]
  29. 29.
    Higgins JP, Soares-Weiser K, López-López JA, Kakourou A, Chaplin K et al. 2016. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ 355:i5170
    [Crossref] [Google Scholar]
  30. 30.
    Aaby P, Rodrigues A, Biai S, Martins C, Veirum JE et al. 2004. Oral polio vaccination and low case fatality at the paediatric ward in Bissau, Guinea-Bissau. Vaccine 22:3014–17
    [Crossref] [Google Scholar]
  31. 31.
    Øland CB, Mogensen SW, Rodrigues A, Benn CS, Aaby P. 2020. Reduced mortality after oral polio vaccination and increased mortality after diphtheria-tetanus-pertussis vaccination in children in a low-income setting. Clin. Ther. 43:1172–84
    [Crossref] [Google Scholar]
  32. 32.
    Ifrim DC, Quintin J, Joosten LA, Jacobs C, Jansen T et al. 2014. Trained immunity or tolerance: opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors. Clin. Vaccine Immunol. 21:534–45
    [Crossref] [Google Scholar]
  33. 33.
    Crișan TO, Cleophas MC, Oosting M, Lemmers H, Toenhake-Dijkstra H et al. 2016. Soluble uric acid primes TLR-induced proinflammatory cytokine production by human primary cells via inhibition of IL-1Ra. Ann. Rheum. Dis. 75:755–62
    [Crossref] [Google Scholar]
  34. 34.
    Barton ES, White DW, Cathelyn JS, Brett-McClellan KA, Engle M et al. 2007. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447:326–29
    [Crossref] [Google Scholar]
  35. 35.
    Sun JC, Beilke JN, Lanier LL. 2009. Adaptive immune features of natural killer cells. Nature 457:557–61
    [Crossref] [Google Scholar]
  36. 36.
    Ishihara C, Mizukoshi N, Iida J, Kato K, Yamamoto K, Azuma I. 1987. Suppression of Sendai virus growth by treatment with Nα-acetylmuramyl-l-alanyl-d-isoglutaminyl-Nε-stearoyl-l-lysine in mice. Vaccine 5:295–301
    [Crossref] [Google Scholar]
  37. 37.
    Spencer JC, Ganguly R, Waldman RH. 1977. Nonspecific protection of mice against influenza virus infection by local or systemic immunization with Bacille Calmette-Guérin. J. Infect. Dis. 136:171–75
    [Crossref] [Google Scholar]
  38. 38.
    Floc'h F, Werner GH 1976. Increased resistance to virus infections of mice inoculated with BCG (Bacillus calmette-guérin). Ann. Immunol. 127:173–86
    [Google Scholar]
  39. 39.
    Starr SE, Visintine AM, Tomeh MO, Nahmias AJ. 1976. Effects of immunostimulants on resistance of newborn mice to herpes simplex type 2 infection. Proc. Soc. Exp. Biol. Med. 152:57–60
    [Crossref] [Google Scholar]
  40. 40.
    Suenaga T, Okuyama T, Yoshida I, Azuma M. 1978. Effect of Mycobacterium tuberculosis BCG infection on the resistance of mice to ectromelia virus infection: participation of interferon in enhanced resistance. Infect. Immun. 20:312–14
    [Crossref] [Google Scholar]
  41. 41.
    Blok BA, Jensen KJ, Aaby P, Fomsgaard A, van Crevel R et al. 2019. Opposite effects of Vaccinia and modified Vaccinia Ankara on trained immunity. Eur. J. Clin. Microbiol. Infect. Dis. 38:449–56
    [Crossref] [Google Scholar]
  42. 42.
    Saeed S, Quintin J, Kerstens HH, Rao NA, Aghajanirefah A et al. 2014. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science 345:1251086
    [Crossref] [Google Scholar]
  43. 43.
    Arts RJW, Moorlag SJCFM, Novakovic B, Li Y, Wang SY et al. 2018. BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host Microbe 23:89–100.e5
    [Crossref] [Google Scholar]
  44. 44.
    Bierman SM. 1976. BCG immunoprophylaxis of recurrent herpes progenitalis. Arch. Dermatol. 112:1410–15
    [Crossref] [Google Scholar]
  45. 45.
    Hippmann G, Wekkeli M, Rosenkranz AR, Jarisch R, Götz M. 1992.. [ Nonspecific immune stimulation with BCG in Herpes simplex recidivans. Follow-up 5 to 10 years after BCG vaccination. ]. Wien. Klin. Wochenschr. 104:2004 (In German)
    [Google Scholar]
  46. 46.
    Douglas JM, Vontver LA, Stamm WE, Reeves WC, Critchlow C et al. 1985. Ineffectiveness and toxicity of BCG vaccine for the prevention of recurrent genital herpes. Antimicrob. Agents Chemother. 27:203–6
    [Crossref] [Google Scholar]
  47. 47.
    Hadden JW. 1993. Immunostimulants.. Trends Pharmacol. Sci. 14:169–74
    [Crossref] [Google Scholar]
  48. 48.
    POLIDIN [drug sheet] Bucuresti, Romania: Institutul Cantacuzino; 2012.
  49. 49.
    Bekkering S, Blok BA, Joosten LA, Riksen NP, van Crevel R, Netea MG. 2016. In vitro experimental model of trained innate immunity in human primary monocytes. Clin. Vaccine Immunol. 23:926–33
    [Crossref] [Google Scholar]
  50. 50.
    Moorlag SJCFM, Rodriguez-Rosales YA, Gillard J, Fanucchi S, Theunissen K et al. 2020. BCG vaccination induces long-term functional reprogramming of human neutrophils. Cell Rep 33:108387
    [Crossref] [Google Scholar]
  51. 51.
    Hammer Q, Romagnani C. 2017. About training and memory: NK-cell adaptation to viral infections. Adv. Immunol. 133:171–207
    [Google Scholar]
  52. 52.
    O'Leary JG, Goodarzi M, Drayton DL, von Andrian UH. 2006. T cell– and B cell–independent adaptive immunity mediated by natural killer cells. Nat. Immunol. 7:507–16
    [Crossref] [Google Scholar]
  53. 53.
    Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Jacobs C et al. 2014. BCG-induced trained immunity in NK cells: role for non-specific protection to infection. Clin. Immunol. 155:213–19
    [Crossref] [Google Scholar]
  54. 54.
    Weizman O-E, Song E, Adams NM, Hildreth AD, Riggan L et al. 2019. Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12. Nat. Immunol. 20:1004–11
    [Crossref] [Google Scholar]
  55. 55.
    Tumpey TM, Chen SH, Oakes JE, Lausch RN. 1996. Neutrophil-mediated suppression of virus replication after herpes simplex virus type 1 infection of the murine cornea. J. Virol. 70:898–904
    [Crossref] [Google Scholar]
  56. 56.
    Zhou J, Stohlman SA, Hinton DR, Marten NW. 2003. Neutrophils promote mononuclear cell infiltration during viral-induced encephalitis. J. Immunol. 170:3331–36
    [Crossref] [Google Scholar]
  57. 57.
    Tate MD, Deng YM, Jones JE, Anderson GP, Brooks AG, Reading PC. 2009. Neutrophils ameliorate lung injury and the development of severe disease during influenza infection. J. Immunol. 183:7441–50
    [Crossref] [Google Scholar]
  58. 58.
    Tate MD, Brooks AG, Reading PC. 2008. The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice. Respir. Res. 9:57
    [Crossref] [Google Scholar]
  59. 59.
    Kaufmann E, Sanz J, Dunn JL, Khan N, Mendonça LE et al. 2018. BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell 172:176–90.e19
    [Crossref] [Google Scholar]
  60. 60.
    Kalafati L, Kourtzelis I, Schulte-Schrepping J, Li X, Hatzioannou A et al. 2020. Innate immune training of granulopoiesis promotes anti-tumor activity. Cell 183:771–85.e12
    [Crossref] [Google Scholar]
  61. 61.
    Kleinnijenhuis J, Quintin J, Preijers F, Benn CS, Joosten LA et al. 2014. Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. J. Innate Immun. 6:152–58
    [Crossref] [Google Scholar]
  62. 62.
    de Castro MJ, Pardo-Seco J, Martinón-Torres F. 2015. Nonspecific (heterologous) protection of neonatal BCG vaccination against hospitalization due to respiratory infection and sepsis. Clin. Infect. Dis. 60:1611–19
    [Crossref] [Google Scholar]
  63. 63.
    Rieckmann A, Villumsen M, Sørup S, Haugaard LK, Ravn H et al. 2017. Vaccinations against smallpox and tuberculosis are associated with better long-term survival: a Danish case-cohort study 1971–2010. Int. J. Epidemiol. 46:695–705
    [Google Scholar]
  64. 64.
    Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC et al. 2012. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. PNAS 109:17537–42
    [Crossref] [Google Scholar]
  65. 65.
    Mitroulis I, Ruppova K, Wang B, Chen L-S, Grzybek M et al. 2018. Modulation of myelopoiesis progenitors is an integral component of trained immunity. Cell 172:147–61.e12
    [Crossref] [Google Scholar]
  66. 66.
    Cirovic B, de Bree LCJ, Groh L, Blok BA, Chan J et al. 2020. BCG vaccination in humans elicits trained immunity via the hematopoietic progenitor compartment. Cell Host Microbe 28:322–34.e5
    [Crossref] [Google Scholar]
  67. 67.
    Leentjens J, Kox M, Stokman R, Gerretsen J, Diavatopoulos DA et al. 2015. BCG vaccination enhances the immunogenicity of subsequent influenza vaccination in healthy volunteers: a randomized, placebo-controlled pilot study. J. Infect. Dis. 212:1930–38
    [Crossref] [Google Scholar]
  68. 68.
    Scheid A, Borriello F, Pietrasanta C, Christou H, Diray-Arce J et al. 2018. Adjuvant effect of Bacille Calmette-Guérin on hepatitis B vaccine immunogenicity in the preterm and term newborn. Front. Immunol. 9:29
    [Crossref] [Google Scholar]
  69. 69.
    McFarland HI, Nahill SR, Maciaszek JW, Welsh RM. 1992. CD11b (Mac-1): a marker for CD8+ cytotoxic T cell activation and memory in virus infection. J. Immunol. 149:1326–33
    [Crossref] [Google Scholar]
  70. 70.
    Quintin J, Saeed S, Martens JHA, Giamarellos-Bourboulis EJ, Ifrim DC et al. 2012. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe 12:223–32
    [Crossref] [Google Scholar]
  71. 71.
    Gumá M, Angulo A, Vilches C, Gómez-Lozano N, Malats N, López-Botet M. 2004. Imprint of human cytomegalovirus infection on the NK cell receptor repertoire. Blood 104:3664–71
    [Crossref] [Google Scholar]
  72. 72.
    Petersen L, Roug AS, Skovbo A, Thysen AH, Eskelund CW, Hokland ME. 2009. The CD94/NKG2C-expressing NK cell subset is augmented in chronic lymphocytic leukemia patients with positive human cytomegalovirus serostatus. Viral Immunol. 22:333–37
    [Crossref] [Google Scholar]
  73. 73.
    Arts RJW, Carvalho A, La Rocca C, Palma C, Rodrigues F et al. 2016. Immunometabolic pathways in BCG-induced trained immunity. Cell Rep 17:2562–71
    [Crossref] [Google Scholar]
  74. 74.
    Bekkering S, Arts RJW, Novakovic B, Kourtzelis I, van der Heijden C et al. 2018. Metabolic induction of trained immunity through the mevalonate pathway. Cell 172:135–46.e9
    [Crossref] [Google Scholar]
  75. 75.
    Fanucchi S, Fok ET, Dalla E, Shibayama Y, Börner K et al. 2019. Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments. Nat. Genet. 51:138–50
    [Crossref] [Google Scholar]
  76. 76.
    Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R et al. 2011. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472:120–24
    [Crossref] [Google Scholar]
  77. 77.
    Novakovic B, Habibi E, Wang S-Y, Arts RJW, Davar R et al. 2016. β-Glucan reverses the epigenetic state of LPS-induced immunological tolerance. Cell 167:1354–68.e14
    [Crossref] [Google Scholar]
  78. 78.
    Kamada R, Yang W, Zhang Y, Patel MC, Yang Y et al. 2018. Interferon stimulation creates chromatin marks and establishes transcriptional memory. PNAS 115:E9162–71
    [Crossref] [Google Scholar]
  79. 79.
    Domínguez-Andrés J, Novakovic B, Li Y, Scicluna BP, Gresnigt MS et al. 2019. The itaconate pathway is a central regulatory node linking innate immune tolerance and trained immunity. Cell Metab 29:211–20.e5
    [Crossref] [Google Scholar]
  80. 80.
    Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A et al. 2020. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe 27:992–1000.e3
    [Crossref] [Google Scholar]
  81. 81.
    Arts RJ, Novakovic B, Ter Horst R, Carvalho A, Bekkering S et al. 2016. Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity. Cell Metab 24:807–19
    [Crossref] [Google Scholar]
  82. 82.
    Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S et al. 2014. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345:1250684
    [Crossref] [Google Scholar]
  83. 83.
    Arts RJ, Joosten LA, Netea MG. 2016. Immunometabolic circuits in trained immunity. Semin. Immunol. 28:425–30
    [Crossref] [Google Scholar]
  84. 84.
    Netea MG, Giamarellos-Bourboulis EJ, Domínguez-Andrés J, Curtis N, van Crevel R et al. 2020. Trained immunity: a tool for reducing susceptibility to and the severity of SARS-CoV-2 infection. Cell 181:969–77
    [Crossref] [Google Scholar]
  85. 85.
    Rivas MN, Ebinger JE, Wu M, Sun N, Braun J et al. 2021. BCG vaccination history associates with decreased SARS-CoV-2 seroprevalence across a diverse cohort of health care workers. J. Clin. Invest. 131:2e145157
    [Crossref] [Google Scholar]
  86. 86.
    Urashima M, Otani K, Hasegawa Y, Akutsu T. 2020. BCG vaccination and mortality of COVID-19 across 173 countries: an ecological study. Int. J. Environ. Res. Public Health 17:155589
    [Crossref] [Google Scholar]
  87. 87.
    Green CM, Fanucchi S, Dominguez-Andres J, Fok ET, Moorlag SJCFM et al. 2020. COVID-19: A model correlating BCG vaccination to protection from mortality implicates trained immunity. medRxiv 2020.04.10.20060905. https://doi.org/10.1101/2020.04.10.20060905
    [Crossref]
  88. 88.
    Ten Doesschate T, Moorlag SJCFM, van der Vaart TW, Taks E, Debisarun P et al. 2020. Two randomized controlled trials of Bacillus Calmette-Guérin vaccination to reduce absenteeism among health care workers and hospital admission by elderly persons during the COVID-19 pandemic: a structured summary of the study protocols for two randomised controlled trials. Trials 21:481
    [Crossref] [Google Scholar]
  89. 89.
    Moorlag SJCFM, van Deuren RC, van Werkhoven CH, Jaeger M, Debisarun P et al. 2020. Safety and COVID-19 symptoms in individuals recently vaccinated with BCG: a retrospective cohort study. Cell Rep. Med. 1:100073
    [Crossref] [Google Scholar]
  90. 90.
    Tsilika M, Taks E, Dolianitis K, Kotsaki A, Leventogiannis K et al. 2021. ACTIVATE-2: a double-blind randomized trial of BCG vaccination against COVID19 in individuals at risk. medRxiv 2021.05.20.21257520. https://doi.org/10.1101/2021.05.20.21257520
    [Crossref]
  91. 91.
    Moorlag SJCFM, Taks E, Ten Doesschate T, van der Vaart TW, Janssen AB et al. 2022. Efficacy of Bacillus Calmette-Guérin vaccination against respiratory tract infections in the elderly during the COVID-19 pandemic. Clin. Infect. Dis. 2022:ciac182
    [Google Scholar]
  92. 92.
    Counoupas C, Johansen MD, Stella AO, Nguyen DH, Ferguson AL et al. 2021. A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection. NPJ Vaccines 6:143
    [Crossref] [Google Scholar]
  93. 93.
    Ramos-Martinez E, Falfán-Valencia R, Pérez-Rubio G, Andrade WA, Rojas-Serrano J et al. 2021. Effect of BCG revaccination on occupationally exposed medical personnel vaccinated against SARS-CoV-2. Cells 10:3179
    [Crossref] [Google Scholar]
  94. 94.
    Debisarun PA, Gössling KL, Bulut O, Kilic G, Zoodsma M et al. 2021. Induction of trained immunity by influenza vaccination—impact on COVID-19. PLOS Pathog. 17:10e1009928
    [Crossref] [Google Scholar]
  95. 95.
    Kyriazopoulou E, Huet T, Cavalli G, Gori A, Kyprianou M et al. 2021. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis. Lancet Rheumatol 3:e690–97
    [Crossref] [Google Scholar]
  96. 96.
    Conlon A, Ashur C, Washer L, Eagle KA, Hofmann Bowman MA 2021. Impact of the influenza vaccine on COVID-19 infection rates and severity. Am. J. Infect. Control 49:694–700
    [Crossref] [Google Scholar]
  97. 97.
    Patwardhan A, Ohler A. 2021. The flu vaccination may have a protective effect on the course of COVID-19 in the pediatric population: When does severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) meet influenza?. Cureus 13:e12533
    [Google Scholar]
  98. 98.
    Fink G, Orlova-Fink N, Schindler T, Grisi S, Ferrer APS et al. 2021. Inactivated trivalent influenza vaccination is associated with lower mortality among patients with COVID-19 in Brazil. BMJ Evid. Based Med. 26:192–93
    [Crossref] [Google Scholar]
  99. 99.
    Fedrizzi EN, Girondi JBR, Sakae TM, Steffens SM, de Souza Silvestrin AN et al. 2021. Efficacy of the measles-mumps-rubella (MMR) vaccine in the reducing the severity of COVID-19: an interim analysis of a randomised controlled clinical trial. medRxiv 2021.09.14.21263598. https://doi.org/10.1101/2021.09.14.21263598
    [Crossref]
  100. 100.
    Mysore V, Cullere X, Settles ML, Ji X, Kattan MW et al. 2021. Protective heterologous T cell immunity in COVID-19 induced by the trivalent MMR and Tdap vaccine antigens. Med 2:1050–71.e7
    [Crossref] [Google Scholar]
  101. 101.
    Bruxvoort KJ, Ackerson B, Sy LS, Bhavsar A, Tseng HF et al. 2021. Recombinant adjuvanted zoster vaccine and reduced risk of COVID-19 diagnosis and hospitalization in older adults. J. Infect. Dis. 2021:jiab633
    [Google Scholar]
  102. 102.
    Habibzadeh F, Sajadi MM, Chumakov K, Yadollahie M, Kottilil S et al. 2021. COVID-19 infection among women in Iran exposed versus unexposed to children who received attenuated poliovirus used in oral polio vaccine. JAMA Netw. Open 4:e2135044
    [Crossref] [Google Scholar]
  103. 103.
    Moorlag SJCFM, Matzaraki V, van Puffelen JH, van der Heijden C, Keating S et al. 2021. An integrative genomics approach identifies KDM4 as a modulator of trained immunity. Eur. J. Immunol. 52:3431–46
    [Crossref] [Google Scholar]
  104. 104.
    Priem B, van Leent MMT, Teunissen AJP, Sofias AM, Mourits VP et al. 2020. Trained immunity-promoting nanobiologic therapy suppresses tumor growth and potentiates checkpoint inhibition. Cell 183:786–801.e19
    [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-virology-091919-072546
Loading
/content/journals/10.1146/annurev-virology-091919-072546
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error