RSV Vaccine-Enhanced Disease Is Orchestrated by the Combined Actions of Distinct CD4 T Cell Subsets

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RSV is a significant healthcare burden and is the leading cause of bronchiolitis and pneumonia during childhood. The failure of the 1960's FI-RSV vaccine trial to not only elicit protection against RSV infection, but also provoke enhanced morbidity and mortality in vaccinees has significantly hampered development of new RSV vaccines for fear of disease potentiation. Therefore we sought to determine the specific immunological mechanisms that mediate FI-RSV VED to provide a framework to evaluate factors associated with disease exacerbation. Work presented herein demonstrate for the first time that individual disease manifestations associated with FI-RSV-immunization are mediated by distinct CD4 T cell subsets and not by eosinophils. Our results stress the need to evaluate multiple disease parameters for future RSV vaccine candidates. Failure to thoroughly assess the immune response and disease manifestations associated with new candidate vaccines may lead to undesired results in vaccine trials and further hinder future vaccine development.

Vyšlo v časopise: RSV Vaccine-Enhanced Disease Is Orchestrated by the Combined Actions of Distinct CD4 T Cell Subsets. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004757
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004757

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1. Heilman CA (1990) From the National Institute of Allergy and Infectious Diseases and the World Health Organization. Respiratory syncytial and parainfluenza viruses. J Infect Dis 161: 402–406. 2155971

2. Shay DK, Holman RC, Roosevelt GE, Clarke MJ, Anderson LJ (2001) Bronchiolitis-associated mortality and estimates of respiratory syncytial virus-associated deaths among US children, 1979–1997. J Infect Dis 183: 16–22. 11076709

3. Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, et al. (2003) Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 289: 179–186. 12517228

4. Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, et al. (1969) Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 89: 422–434. 4305198

5. Chin J, Magoffin RL, Shearer LA, Schieble JH, Lennette EH (1969) Field evaluation of a respiratory syncytial virus vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. Am J Epidemiol 89: 449–463. 4305200

6. Fulginiti VA, Eller JJ, Sieber OF, Joyner JW, Minamitani M, et al. (1969) Respiratory virus immunization. I. A field trial of two inactivated respiratory virus vaccines; an aqueous trivalent parainfluenza virus vaccine and an alum-precipitated respiratory syncytial virus vaccine. Am J Epidemiol 89: 435–448. 4305199

7. Weibel RE, Stokes J Jr., Leagus MB, Mascoli CC, Tytell AA, et al. (1967) Respiratory virus vaccines. VII. Field evaluation of respiratory syncytial, parainfluenza 1, 2, 3, and Mycoplasma pneumoniae vaccines, 1965 to 1966. Am Rev Respir Dis 96: 724–739. 4293644

8. Kapikian AZ, Mitchell RH, Chanock RM, Shvedoff RA, Stewart CE (1969) An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. Am J Epidemiol 89: 405–421. 4305197

9. Waris ME, Tsou C, Erdman DD, Zaki SR, Anderson LJ (1996) Respiratory synctial virus infection in BALB/c mice previously immunized with formalin-inactivated virus induces enhanced pulmonary inflammatory response with a predominant Th2-like cytokine pattern. J Virol 70: 2852–2860. 8627759

10. Johnson TR, Graham BS (1999) Secreted respiratory syncytial virus G glycoprotein induces interleukin-5 (IL-5), IL-13, and eosinophilia by an IL-4-independent mechanism. J Virol 73: 8485–8495. 10482601

11. Kakuk TJ, Soike K, Brideau RJ, Zaya RM, Cole SL, et al. (1993) A human respiratory syncytial virus (RSV) primate model of enhanced pulmonary pathology induced with a formalin-inactivated RSV vaccine but not a recombinant FG subunit vaccine. J Infect Dis 167: 553–561. 8440926

12. Prince GA, Curtis SJ, Yim KC, Porter DD (2001) Vaccine-enhanced respiratory syncytial virus disease in cotton rats following immunization with Lot 100 or a newly prepared reference vaccine. J Gen Virol 82: 2881–2888. 11714962

13. Polack FP, Teng MN, Collins PL, Prince GA, Exner M, et al. (2002) A role for immune complexes in enhanced respiratory syncytial virus disease. J Exp Med 196: 859–865. 12235218

14. Delgado MF, Coviello S, Monsalvo AC, Melendi GA, Hernandez JZ, et al. (2009) Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease. Nat Med 15: 34–41. doi: 10.1038/nm.1894 19079256

15. Sanders CJ, Vogel P, McClaren JL, Bajracharya R, Doherty PC, et al. (2013) Compromised respiratory function in lethal influenza infection is characterized by the depletion of type I alveolar epithelial cells beyond threshold levels. Am J Physiol Lung Cell Mol Physiol 304: L481–488. doi: 10.1152/ajplung.00343.2012 23355384

16. Morrey JD, Siddharthan V, Wang H, Hall JO (2012) Respiratory insufficiency correlated strongly with mortality of rodents infected with West Nile virus. PLoS One 7: e38672. doi: 10.1371/journal.pone.0038672 22719920

17. van Schaik SM, Enhorning G, Vargas I, Welliver RC (1998) Respiratory syncytial virus affects pulmonary function in BALB/c mice. J Infect Dis 177: 269–276. 9466511

18. Huck B, Neumann-Haefelin D, Schmitt-Graeff A, Weckmann M, Mattes J, et al. (2007) Human metapneumovirus induces more severe disease and stronger innate immune response in BALB/c mice as compared with respiratory syncytial virus. Respir Res 8: 6. 17257445

19. Yu C, Cantor AB, Yang H, Browne C, Wells RA, et al. (2002) Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. J Exp Med 195: 1387–1395. 12045237

20. Connors M, Kulkarni AB, Firestone CY, Holmes KL, Morse HC 3rd, et al. (1992) Pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of CD4+ T cells. J Virol 66: 7444–7451. 1433525

21. Olson MR, Varga SM (2007) CD8 T cells inhibit respiratory syncytial virus (RSV) vaccine-enhanced disease. J Immunol 179: 5415–5424. 17911628

22. Olson MR, Hartwig SM, Varga SM (2008) The number of respiratory syncytial virus (RSV)-specific memory CD8 T cells in the lung is critical for their ability to inhibit RSV vaccine-enhanced pulmonary eosinophilia. J Immunol 181: 7958–7968. 19017987

23. Wurster AL, Tanaka T, Grusby MJ (2000) The biology of Stat4 and Stat6. Oncogene 19: 2577–2584. 10851056

24. Ochkur SI, Jacobsen EA, Protheroe CA, Biechele TL, Pero RS, et al. (2007) Coexpression of IL-5 and eotaxin-2 in mice creates an eosinophil-dependent model of respiratory inflammation with characteristics of severe asthma. J Immunol 178: 7879–7889. 17548626

25. Spry CJ (1989) The pathogenesis of endomyocardial fibrosis: the role of the eosinophil. Springer Semin Immunopathol 11: 471–477. 2694412

26. Tai PC, Ackerman SJ, Spry CJ, Dunnette S, Olsen EG, et al. (1987) Deposits of eosinophil granule proteins in cardiac tissues of patients with eosinophilic endomyocardial disease. Lancet 1: 643–647. 2882081

27. Kay AB, Phipps S, Robinson DS (2004) A role for eosinophils in airway remodelling in asthma. Trends Immunol 25: 477–482. 15324740

28. Lukens MV, van de Pol AC, Coenjaerts FE, Jansen NJ, Kamp VM, et al. (2010) A systemic neutrophil response precedes robust CD8(+) T-cell activation during natural respiratory syncytial virus infection in infants. J Virol 84: 2374–2383. doi: 10.1128/JVI.01807-09 20015982

29. Phipps S, Lam CE, Mahalingam S, Newhouse M, Ramirez R, et al. (2007) Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus. Blood 110: 1578–1586. 17495130

30. Castilow EM, Meyerholz DK, Varga SM (2008) IL-13 is required for eosinophil entry into the lung during respiratory syncytial virus vaccine-enhanced disease. J Immunol 180: 2376–2384. 18250447

31. Johnson TR, Rothenberg ME, Graham BS (2008) Pulmonary eosinophilia requires interleukin-5, eotaxin-1, and CD4+ T cells in mice immunized with respiratory syncytial virus G glycoprotein. J Leukoc Biol 84: 748–759. doi: 10.1189/jlb.0907621 18519743

32. Tanaka H, Komai M, Nagao K, Ishizaki M, Kajiwara D, et al. (2004) Role of interleukin-5 and eosinophils in allergen-induced airway remodeling in mice. Am J Respir Cell Mol Biol 31: 62–68. 14975941

33. Humbles AA, Lloyd CM, McMillan SJ, Friend DS, Xanthou G, et al. (2004) A critical role for eosinophils in allergic airways remodeling. Science 305: 1776–1779. 15375268

34. Bell SJ, Metzger WJ, Welch CA, Gilmour MI (1996) A role for Th2 T-memory cells in early airway obstruction. Cell Immunol 170: 185–194. 8660817

35. Cohn L, Homer RJ, MacLeod H, Mohrs M, Brombacher F, et al. (1999) Th2-induced airway mucus production is dependent on IL-4Ralpha, but not on eosinophils. J Immunol 162: 6178–6183. 10229862

36. Brightling CE, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID, et al. (2003) Interleukin-4 and -13 expression is co-localized to mast cells within the airway smooth muscle in asthma. Clin Exp Allergy 33: 1711–1716. 14656359

37. Barnes PJ (2008) Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 8: 183–192. doi: 10.1038/nri2254 18274560

38. Mukhopadhyay S, Hoidal JR, Mukherjee TK (2006) Role of TNFalpha in pulmonary pathophysiology. Respir Res 7: 125. 17034639

39. Kampf C, Relova AJ, Sandler S, Roomans GM (1999) Effects of TNF-alpha, IFN-gamma and IL-beta on normal human bronchial epithelial cells. Eur Respir J 14: 84–91. 10489833

40. Boulet LP, Turcotte H, Brochu A (1994) Persistence of airway obstruction and hyperresponsiveness in subjects with asthma remission. Chest 105: 1024–1031. 8162720

41. Bacharier LB, Strunk RC, Mauger D, White D, Lemanske RF Jr., et al. (2004) Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function. Am J Respir Crit Care Med 170: 426–432. 15172893

42. Fuhlbrigge AL, Kitch BT, Paltiel AD, Kuntz KM, Neumann PJ, et al. (2001) FEV(1) is associated with risk of asthma attacks in a pediatric population. J Allergy Clin Immunol 107: 61–67. 11149992

43. (2000) Long-term effects of budesonide or nedocromil in children with asthma. The Childhood Asthma Management Program Research Group. N Engl J Med 343: 1054–1063. 11027739

44. Matthys P, Billiau A (1997) Cytokines and cachexia. Nutrition 13: 763–770. 9290087

45. Tisdale MJ (1997) Biology of cachexia. J Natl Cancer Inst 89: 1763–1773. 9392617

46. Rutigliano JA, Graham BS (2004) Prolonged production of TNF-alpha exacerbates illness during respiratory syncytial virus infection. J Immunol 173: 3408–3417. 15322205

47. Seki E, Yoshizumi M, Tanaka R, Ryo A, Ishioka T, et al. (2013) Cytokine profiles, signalling pathways and effects of fluticasone propionate in respiratory syncytial virus-infected human foetal lung fibroblasts. Cell Biol Int.

48. Connors M, Giese NA, Kulkarni AB, Firestone CY, Morse HC 3rd, et al. (1994) Enhanced pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of interleukin-4 (IL-4) and IL-10. J Virol 68: 5321–5325. 8035532

49. Kwilas S, Liesman RM, Zhang L, Walsh E, Pickles RJ, et al. (2009) Respiratory syncytial virus grown in Vero cells contains a truncated attachment protein that alters its infectivity and dependence on glycosaminoglycans. J Virol 83: 10710–10718. doi: 10.1128/JVI.00986-09 19656891

50. Johnson TR, Teng MN, Collins PL, Graham BS (2004) Respiratory syncytial virus (RSV) G glycoprotein is not necessary for vaccine-enhanced disease induced by immunization with formalin-inactivated RSV. J Virol 78: 6024–6032. 15141000

51. Irvin CG, Bates JH (2003) Measuring the lung function in the mouse: the challenge of size. Respir Res 4: 4. 12783622

52. Weiss KA, Christiaansen AF, Fulton RB, Meyerholz DK, Varga SM (2011) Multiple CD4+ T cell subsets produce immunomodulatory IL-10 during respiratory syncytial virus infection. J Immunol 187: 3145–3154. doi: 10.4049/jimmunol.1100764 21844390

53. Bates J, Irvin C, Brusasco V, Drazen J, Fredberg J, et al. (2004) The use and misuse of Penh in animal models of lung disease. Am J Respir Cell Mol Biol 31: 373–374. 15317683

54. Collins RA, Gualano RC, Zosky GR, Atkins CL, Turner DJ, et al. (2005) Hyperresponsiveness to inhaled but not intravenous methacholine during acute respiratory syncytial virus infection in mice. Respir Res 6: 142. 16324223

55. Aeffner F, Davis IC (2012) Respiratory syncytial virus reverses airway hyperresponsiveness to methacholine in ovalbumin-sensitized mice. PLoS One 7: e46660. doi: 10.1371/journal.pone.0046660 23056391

56. Stokes KL, Chi MH, Sakamoto K, Newcomb DC, Currier MG, et al. (2011) Differential pathogenesis of respiratory syncytial virus clinical isolates in BALB/c mice. J Virol 85: 5782–5793. doi: 10.1128/JVI.01693-10 21471228

57. You D, Becnel D, Wang K, Ripple M, Daly M, et al. (2006) Exposure of neonates to respiratory syncytial virus is critical in determining subsequent airway response in adults. Respir Res 7: 107. 16893457

58. Fulton RB, Meyerholz DK, Varga SM (2010) Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection. J Immunol 185: 2382–2392. doi: 10.4049/jimmunol.1000423 20639494

59. Castilow EM, Olson MR, Meyerholz DK, Varga SM (2008) Differential role of gamma interferon in inhibiting pulmonary eosinophilia and exacerbating systemic disease in fusion protein-immunized mice undergoing challenge infection with respiratory syncytial virus. J Virol 82: 2196–2207. 18094193

60. Gibson-Corley KN, Olivier AK, Meyerholz DK (2013) Principles for valid histopathologic scoring in research. Vet Pathol 50: 1007–1015. doi: 10.1177/0300985813485099 23558974