본문 바로가기
KERD
논문KCI 등재

Intranasal Vaccination with Outer-Membrane Protein of Orientia tsutsugamushi induces Protective Immunity Against Scrub Typhus

2

조회

0

다운로드

1

인용

0

참고문헌

키워드

초록

Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. Since it has been reported that pneumonia is frequently observed in patients with scrub typhus, we investigated whether intranasal (i.n.) vaccination with the outer membrane protein of O. tsutsugamushi (OMPOT) would induce a protective immunity against O. tsutsugamushi infection. It was particular interest that when mice were infected with O. tsutsugamushi, the bacteria disseminated into the lungs, causing pneumonia. The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. The anti-O. tsutsugamushi IgA Abs in BAL fluid after the vaccination showed a high correlation of the protection against O. tsutsugamushi. The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. In conclusion, the current study demonstrated that i.n. vaccination with OMPOT elicited protective immunity against scrub typhus in mouse with O. tsutsugamushi infection causing subsequent pneumonia.

Abstract

Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. Since it has been reported that pneumonia is frequently observed in patients with scrub typhus, we investigated whether intranasal (i.n.) vaccination with the outer membrane protein of O. tsutsugamushi (OMPOT) would induce a protective immunity against O. tsutsugamushi infection. It was particular interest that when mice were infected with O. tsutsugamushi, the bacteria disseminated into the lungs, causing pneumonia. The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. The anti-O. tsutsugamushi IgA Abs in BAL fluid after the vaccination showed a high correlation of the protection against O. tsutsugamushi. The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. In conclusion, the current study demonstrated that i.n. vaccination with OMPOT elicited protective immunity against scrub typhus in mouse with O. tsutsugamushi infection causing subsequent pneumonia.

참고문헌 (59)

  1. Seong SY, "Orientia tsutsugamushi infection : overview and immune responses", Microbes Infect, 3, pp.11~21 (2001)
  2. Chattopadhyay S, "Scrub typhus vaccines : past history and recent developments", Hum Vaccin, 3, pp.73~80 (2007)
  3. Watt G, "Scrub typhus and tropical rickettsioses", Curr Opin Infect Dis, 16, pp.429~436 (2003)
  4. Kelly DJ, "Scrub typhus : the geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi", Clin Infect Dis, 48(Suppl 3), pp.S203~S230 (2009)
  5. Watt G, "Scrub typhus infections poorly responsive to antibiotics in northern Thailand", Lancet, 348, pp.86~89 (1996)
  6. Asadi Karam MR, "Use of flagellin and cholera toxin as adjuvants in intranasal vaccination of mice to enhance protective immune responses against uropathogenic Escherichia coli antigens", Biologicals, 44, pp.378~386 (2016)
  7. Fulton F, "Cultivation of Rickettsia tsutsugamushi in lungs of rodents; preparation of a scrub-typhus vaccine", Lancet, 2, pp.729~734 (1945)
  8. Chattopadhyay S, "Scrub typhus vaccine candidate Kp r56 induces humoral and cellular immune responses in cynomolgus monkeys", Infect Immun, 73, pp.5039~5047 (2005)
  9. Varghese GM, "Clinical profile and improving mortality trend of scrub typhus in South India", Int J Infect Dis, 23, pp.39~43 (2014)
  10. Hsu YH, "Pulmonary pathology in patients associated with scrub typhus", Pathology, 40, pp.268~271 (2008)
  11. Moron CG, "Identification of the target cells of Orientia tsutsugamushi in human cases of scrub typhus", Mod Pathol, 14, pp.752~759 (2001)
  12. Urakami H, "Penetration of Rickettsia tsutsugamushi into cultured mouse fibroblasts(L cells) : an electron microscopic observation", Microbiol Immunol, 27, pp.251~263 (1983)
  13. Song Sun Wha, "Clinical Role of Interstitial Pneumonia in Patients with Scrub Typhus: A Possible Marker of Disease Severity", Journal of Korean Medical Science, 19(5), pp.668~673 (2004), 대한의학회
  14. Chan CH, "Scrub typhus pneumonitis with delayed resolution", J Trop Med Hyg, 98, pp.114~116 (1995)
  15. Chayakul P, "Scrub typhus pneumonitis : an entity which is frequently missed", Q J Med, 68, pp.595~602 (1988)
  16. Smadel JE, "Immunization against scrub typhus : duration of immunity in volunteers following combined living vaccine and chemoprophylaxis", Am J Trop Med Hyg, 1, pp.87~99 (1952)
  17. Ni YS, "Protection against scrub typhus by a plasmid vaccine encoding the 56-KD outer membrane protein antigen gene", Am J Trop Med Hyg, 73, pp.936~941 (2005)
  18. Trent B, "Polarized lung inflammation and Tie2", angiopoietin-mediated endothelial dysfunction during severe Orientia tsutsugamushi infection, 2020, pp.14, e0007675~
  19. Trent B, "Scrub typhus pathogenesis : innate immune response and lung injury during Orientia tsutsugamushi infection", Front Microbiol, 10, pp.2065~ (2019)
  20. Kim HI, "Immunization with a recombinant antigen composed of conserved blocks from TSA56 provides broad genotype protection against scrub typhus", Emerg Microbes Infect, 8, pp.946~958 (2019)
  21. Ha NY, "Longevity of antibody and T-cell responses against outer membrane antigens of Orientia tsutsugamushi in scrub typhus patients", Emerg Microbes Infect, 6, pp.e116~ (2017)
  22. Choi S, "A recombinant 47-kDa outer membrane protein induces an immune response against Orientia tsutsugamushi strain Boryong", Am J Trop Med Hyg, 97, pp.30~37 (2017)
  23. Yu Y, "Induction of protective immunity against scrub typhus with a 56-kilodalton recombinant antigen fused with a 47-kilodalton antigen of Orientia tsutsugamushi Karp", Am J Trop Med Hyg, 72, pp.458~464 (2005)
  24. Chen HW, "Kinetics and magnitude of antibody responses against the conserved 47-kilodalton antigen and the variable 56-kilodalton antigen in scrub typhus patients", Clin Vaccine Immunol, 18, pp.1021~1027 (2011)
  25. Hickman CJ, "Murine T-cell response to native and recombinant protein antigens of Rickettsia tsutsugamushi", Infect Immun, 61, pp.1674~1681 (1993)
  26. Oaks EV, "Antigenic and genetic relatedness of eight Rickettsia tsutsugamushi antigens", Infect Immun, 57, pp.3116~3122 (1989)
  27. Chen HW, "Identification of cross-reactive epitopes on the conserved 47-kilodalton antigen of Orientia tsutsugamushi and human serine protease", Infect Immun, 77, pp.2311~2319 (2009)
  28. 주혁, "Orientia tsutsugamushi Infection Induces CD4+ T Cell Activation via Human Dendritic Cell Activity", Journal of Microbiology and Biotechnology, 23(8), pp.1159~1166 (2013), 한국미생물·생명공학회[DOI]
  29. Tamura A, "Easy method for infectivity titration of Rickettsia tsutsugamushi by infected cell counting(author's transl)", Nippon Saikingaku Zasshi, 36, pp.783~785 (1981)
  30. Ha NY, "Immunization with an autotransporter protein of Orientia tsutsugamushi provides protective immunity against scrub typhus", PLoS Negl Trop Dis, 9, pp.e0003585~ (2015)
  31. Min CK, "A type I interferon and IL-10 induced by Orientia tsutsugamushi infection suppresses antigen-specific T cells and their memory responses", Front Immunol, 9, pp.2022~ (2018)
  32. Aida Y, "Removal of endotoxin from protein solutions by phase separation using Triton X-114", J Immunol Methods, 132, pp.191~195 (1990)
  33. Kim DM, "Effects of antibiotic treatment on the results of nested PCRs for scrub typhus", J Clin Microbiol, 46, pp.3465~3466 (2008)
  34. Park SM, "MyD88 signaling is not essential for induction of antigen-specific B cell responses but is indispensable for protection against Streptococcus pneumoniae infection following oral vaccination with attenuated Salmonella expressing PspA antigen", J Immunol, 181, pp.6447~6455 (2008)
  35. Shim BS, "Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus", polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses, 2010, pp.11, 65~
  36. Chen CH, "Scrub typhus pneumonitis", QJM, 104, pp.537~538 (2011)
  37. Premaratna R, "Rickettsial infections and their clinical presentations in the Western Province of Sri Lanka : a hospital-based study", Int J Infect Dis, 12, pp.198~202 (2008)
  38. Fukuyama Y, "Nasal administration of cholera toxin as a mucosal adjuvant damages the olfactory system in mice", PLoS One, 10, pp.e0139368~ (2015)
  39. Hanson BA, "Effect of immune serum on infectivity of Rickettsia tsutsugamushi", Infect Immun, 42, pp.341~349 (1983)
  40. Hauptmann M, "Protective and pathogenic roles of CD8+ T lymphocytes in murine Orientia tsutsugamushi infection", PLoS Negl Trop Dis, 10, pp.e0004991~ (2016)
  41. Jerrells TR, "Role of T-lymphocytes in production of antibody to antigens of Rickettsia tsutsugamushi and other Rickettsia species", Infect Immun, 41, pp.666~674 (1983)
  42. Forbes EK, "Multifunctional, high-level cytokine-producing Th1 cells in the lung, but not spleen, correlate with protection against Mycobacterium tuberculosis aerosol challenge in mice", J Immunol, 181, pp.4955~4964 (2008)
  43. Lindenstrøm T, "Tuberculosis subunit vaccination provides long-term protective immunity characterized by multifunctional CD4 memory T cells", J Immunol, 182, pp.8047~8055 (2009)
  44. Huster KM, "Protective immunity towards intracellular pathogens", Curr Opin Immunol, 18, pp.458~464 (2006)
  45. Neutra MR, "Mucosal vaccines : the promise and the challenge", Nat Rev Immunol, 6, pp.148~158 (2006)
  46. Peter JV, "Severe scrub typhus infection : clinical features, diagnostic challenges and management", World J Crit Care Med, 4, pp.244~250 (2015)
  47. Seong SY, "Induction of homologous immune response to Rickettsia tsutsugamushi Boryong with a partial 56-kilodalton recombinant antigen fused with the maltose-binding protein MBP-Bor56", Infect Immun, 65, pp.1541~1545 (1997)
  48. Nacy CA, "Macrophages in resistance to rickettsial infection : macrophage activation in vitro for killing of Rickettsia tsutsugamushi", J Immunol, 123, pp.2544~2549 (1979)
  49. Hanson B, "Susceptibility of Rickettsia tsutsugamushi Gilliam to gamma interferon in cultured mouse cells", Infect Immun, 59, pp.4125~4133 (1991)
  50. Walker DH, "Cytokine-induced, nitric oxidedependent, intracellular antirickettsial activity of mouse endothelial cells", Lab Invest, 76, pp.129~138 (1997)
  51. Kodama K, "Establishment and characterization of a T-cell line specific for Rickettsia tsutsugamushi", Infect Immun, 55, pp.2490~2495 (1987)
  52. Woolard MD, "Respiratory Francisella tularensis live vaccine strain infection induces Th17 cells and prostaglandin E2, which inhibits generation of gamma interferonpositive T cells", Infect Immun, 76, pp.2651~2659 (2008)
  53. Zhang X, "A MyD88-dependent early IL-17 production protects mice against airway infection with the obligate intracellular pathogen Chlamydia muridarum", J Immunol, 183, pp.1291~1300 (2009)
  54. Mortensen R, "Local Th17", IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes, 2017, pp.12, e0175707~
  55. Lindenstrøm T, "Vaccine-induced th17 cells are maintained long-term postvaccination as a distinct and phenotypically stable memory subset", Infect Immun, 80, pp.3533~3544 (2012)
  56. Valbuena G, "Approaches to vaccines against Orientia tsutsugamushi", Front Cell Infect Microbiol, 2, pp.170~ (2013)
  57. Kundin WD, "Pathogenesis of scrub typhus infection(Rickettsia tsutsugamushi)as studied by immunofluorescence", J Immunol, 93, pp.772~781 (1964)
  58. "PLoS Negl Trop Dis", 2014, e2966~
  59. Boyaka PN, "Inducing mucosal IgA : a challenge for vaccine adjuvants and delivery systems", J Immunol, 199, pp.9~16 (2017)

이 간행물의 다른 논문 (5건)