본문 바로가기
KERD
논문KCI 등재

Intranasal Immunization With Nanoparticles Containing an Orientia tsutsugamushi Protein Vaccine Candidate and a Polysorbitol Transporter Adjuvant Enhances Both Humoral and Cellular Immune Responses

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

Scrub typhus, a mite-borne infectious disease, is caused by Orientia tsutsugamushi. Despite many attempts to develop a protective strategy, an effective preventive vaccine has not been developed. The identification of appropriate Ags that cover diverse antigenic strains and provide long-lasting immunity is a fundamental challenge in the development of a scrub typhus vaccine. We investigated whether this limitation could be overcome by harnessing the nanoparticle-forming polysorbitol transporter (PST) for an O. tsutsugamushi vaccine strategy. Two target proteins, 56-kDa type-specific Ag (TSA56) and surface cell Ag A (ScaA) were used as vaccine candidates. PST formed stable nano-size complexes with TSA56 (TSA56-PST) and ScaA (ScaA-PST); neither exhibited cytotoxicity. The formation of Ag-specific IgG2a, IgG2b, and IgA in mice was enhanced by intranasal vaccination with TSA56-PST or ScaA-PST. The vaccines containing PST induced Ag-specific proliferation of CD8+ and CD4+ T cells. Furthermore, the vaccines containing PST improved the mouse survival against O. tsutsugamushi infection. Collectively, the present study indicated that PST could enhance both Ag-specific humoral immunity and T cell response, which are essential to effectively confer protective immunity against O. tsutsugamushi infection. These findings suggest that PST has potential for use in an intranasal vaccination strategy.

Abstract

Scrub typhus, a mite-borne infectious disease, is caused by Orientia tsutsugamushi. Despite many attempts to develop a protective strategy, an effective preventive vaccine has not been developed. The identification of appropriate Ags that cover diverse antigenic strains and provide long-lasting immunity is a fundamental challenge in the development of a scrub typhus vaccine. We investigated whether this limitation could be overcome by harnessing the nanoparticle-forming polysorbitol transporter (PST) for an O. tsutsugamushi vaccine strategy. Two target proteins, 56-kDa type-specific Ag (TSA56) and surface cell Ag A (ScaA) were used as vaccine candidates. PST formed stable nano-size complexes with TSA56 (TSA56-PST) and ScaA (ScaA-PST); neither exhibited cytotoxicity. The formation of Ag-specific IgG2a, IgG2b, and IgA in mice was enhanced by intranasal vaccination with TSA56-PST or ScaA-PST. The vaccines containing PST induced Ag-specific proliferation of CD8+ and CD4+ T cells. Furthermore, the vaccines containing PST improved the mouse survival against O. tsutsugamushi infection. Collectively, the present study indicated that PST could enhance both Ag-specific humoral immunity and T cell response, which are essential to effectively confer protective immunity against O. tsutsugamushi infection. These findings suggest that PST has potential for use in an intranasal vaccination strategy.

참고문헌 (57)

  1. Xu G, "A review of the global epidemiology of scrub typhus", PLoS Negl Trop Dis, 11, pp.e0006062~ (2017)
  2. Luce-Fedrow A, "A review of scrub typhus(Orientia tsutsugamushi and related organisms) : then, now, and tomorrow", Trop Med Infect Dis, 3, pp.8~ (2018)
  3. Kala D, "Diagnosis of scrub typhus : recent advancements and challenges", 3 Biotech, 10, pp.396~ (2020)
  4. Banerjee A, "Orientia tsutsugamushi : the dangerous yet neglected foe from the East", Int J Med Microbiol, 311, pp.151467~ (2021)
  5. Valbuena G, "Approaches to vaccines against Orientia tsutsugamushi", Front Cell Infect Microbiol, 2, pp.170~ (2013)
  6. 박성무, "Intranasal Vaccination with Outer-Membrane Protein of Orientia tsutsugamushi induces Protective Immunity Against Scrub Typhus", Immune Network, 21(2), pp.1~17 (2021), 대한면역학회[DOI]
  7. Basharat Z, "Differential analysis of Orientia tsutsugamushi genomes for therapeutic target identification and possible intervention through natural product inhibitor screening", Comput Biol Med, 141, pp.105165~ (2022)
  8. Ha NY, "Immunization with an autotransporter protein of Orientia tsutsugamushi provides protective immunity against scrub typhus", PLoS Negl Trop Dis, 9, pp.e0003585~ (2015)
  9. Ha NY, "Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen", J Nanobiotechnology, 14, pp.76~ (2016)
  10. 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)
  11. Chattopadhyay S, "Scrub typhus vaccines : past history and recent developments", Hum Vaccin, 3, pp.73~80 (2007)
  12. Koralur MC, "Detection and distribution of Sca autotransporter protein antigens in diverse isolates of Orientia tsutsugamushi", PLoS Negl Trop Dis, 12, pp.e0006784~ (2018)
  13. Cho BA, "Intracellular invasion by Orientia tsutsugamushi is mediated by integrin signaling and actin cytoskeleton rearrangements", Infect Immun, 78, pp.1915~1923 (2010)
  14. Lee JH, "Fibronectin facilitates the invasion of Orientia tsutsugamushi into host cells through interaction with a 56-kDa type-specific antigen", J Infect Dis, 198, pp.250~257 (2008)
  15. Cai T, "Delivery of nanovaccine towards lymphoid organs : recent strategies in enhancing cancer immunotherapy", J Nanobiotechnology, 19, pp.389~ (2021)
  16. Zhang Y, "Nanovaccines for cancer immunotherapy", Wiley Interdiscip Rev Nanomed Nanobiotechnol, 11, pp.e1559~ (2019)
  17. Jiang H, "Lymph node targeting strategies to improve vaccination efficacy", J Control Release, 267, pp.47~56 (2017)
  18. Kim CG, "The role of nanovaccine in cross-presentation of antigen-presenting cells for the activation of CD8+ T cell responses", Pharmaceutics, 11, pp.612~ (2019)
  19. Firdous J, "Induction of long-term immunity against respiratory syncytial virus glycoprotein by an osmotic polymeric nanocarrier", Acta Biomater, 10, pp.4606~4617 (2014)
  20. Kye YC, "Intranasal immunization with pneumococcal surface protein A in the presence of nanoparticle forming polysorbitol transporter adjuvant induces protective immunity against the Streptococcus pneumoniae infection", Acta Biomater, 90, pp.362~372 (2019)
  21. Paramithiotis E, "Cellular immunity is critical for assessing COVID-19 vaccine effectiveness in immunocompromised individuals", Front Immunol, 13, pp.880784~ (2022)
  22. Griffiths KL, "Novel vaccine approaches for protection against intracellular pathogens", Curr Opin Immunol, 28, pp.58~63 (2014)
  23. Hauptmann M, "Protective and pathogenic roles of CD8+ T lymphocytes in murine Orientia tsutsugamushi infection", PLoS Negl Trop Dis, 10, pp.e0004991~ (2016)
  24. Xu G, "CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection", PLoS Negl Trop Dis, 11, pp.e0005763~ (2017)
  25. Kim HW, "Galectin-9induced by dietary probiotic mixture regulates immune balance to reduce atopic dermatitis symptoms in mice", Front Immunol, 10, pp.3063~ (2020)
  26. 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]
  27. Tamura A, "Easy method for infectivity titration of Rickettsia tsutsugamushi by infected cell counting", Nippon Saikingaku Zasshi, 36, pp.783~785 (1981)
  28. 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)
  29. Bhat P, "Interferon-γ derived from cytotoxic lymphocytes directly enhances their motility and cytotoxicity", Cell Death Dis, 8, pp.e2836~ (2017)
  30. Sumonwiriya M, "Strong interferon-gamma mediated cellular immunity to scrub typhus demonstrated using a novel whole cell antigen ELISpot assay in rhesus macaques and humans", PLoS Negl Trop Dis, 11, pp.e0005846~ (2017)
  31. Seong SY, "Orientia tsutsugamushi infection : overview and immune responses", Microbes Infect, 3, pp.11~21 (2001)
  32. Farber DL, "Human memory T cells : generation, compartmentalization and homeostasis", Nat Rev Immunol, 14, pp.24~35 (2014)
  33. Sasaki K, "Activated-memory T cells influence naïve T cell fate : a noncytotoxic function of human CD8 T cells", Commun Biol, 5, pp.634~ (2022)
  34. Tarke A, "SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron", Cell, 185, pp.847~859 (2022)
  35. Hemmi T, "Intranasal vaccination induced cross-protective secretory IgA antibodies against SARS-CoV-2 variants with reducing the potential risk of lung eosinophilic immunopathology", Vaccine, 40, pp.5892~5903 (2022)
  36. Li L, "Mucosal IgA response elicited by intranasal immunization of Lactobacillus plantarum expressing surface-displayed RBD protein of SARSCoV-2", Int J Biol Macromol, 190, pp.409~416 (2021)
  37. "PLoS Negl Trop Dis", 2014, e2966~
  38. Trent B, "Scrub Typhus Pathogenesis : Innate Immune Response and Lung Injury During Orientia tsutsugamushi Infection", Front Microbiol, 10, pp.2065~ (2019)
  39. Trent B, "Polarized lung inflammation and Tie2", angiopoietin-mediated endothelial dysfunction during severe Orientia tsutsugamushi infection, 2020, pp.14, e0007675~
  40. Atwal S, "The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state", Nat Commun, 13, pp.3603~ (2022)
  41. Liu J, "Vaccines elicit highly conserved cellular immunity to SARS-CoV-2 Omicron", Nature, 603, pp.493~496 (2022)
  42. Farhood B, "CD8+ cytotoxic T lymphocytes in cancer immunotherapy : a review", J Cell Physiol, 234, pp.8509~8521 (2019)
  43. Kuznetsova M, "Cytotoxic activity and memory T cell subset distribution of in vitro-stimulated CD8+ T cells specific for HER2", neu epitopes, 2019, pp.10, 1017~
  44. Hillaire Marine Laure Bettina, "IFN-γ: A Crucial Player in the Fight Against HBV Infection?", Immune Network, 23(4), pp.1~18 (2023), 대한면역학회[DOI]
  45. Kiniry BE, "Differential expression of CD8+ T cell cytotoxic effector molecules in blood and gastrointestinal mucosa in HIV-1 infection", J Immunol, 200, pp.1876~1888 (2018)
  46. Zöphel D, "Faster cytotoxicity with age : Increased perforin and granzyme levels in cytotoxic CD8+ T cells boost cancer cell elimination", Aging Cell, 21, pp.e13668~ (2022)
  47. Aktas E, "Relationship between CD107a expression and cytotoxic activity", Cell Immunol, 254, pp.149~154 (2009)
  48. Green AM, "IFN-γ from CD4 T cells is essential for host survival and enhances CD8 T cell function during Mycobacterium tuberculosis infection", J Immunol, 190, pp.270~277 (2013)
  49. Topchyan Paytsar, "The Role of CD4 T Cell Help in CD8 T Cell Differentiation and Function During Chronic Infection and Cancer", Immune Network, 23(5), pp.1~21 (2023), 대한면역학회[DOI]
  50. Bousso P, "T-cell activation by dendritic cells in the lymph node : lessons from the movies", Nat Rev Immunol, 8, pp.675~684 (2008)
  51. Guermonprez P, "Antigen presentation and T cell stimulation by dendritic cells", Annu Rev Immunol, 20, pp.621~667 (2002)
  52. Pooley JL, "Cutting edge : intravenous soluble antigen is presented to CD4 T cells by CD8-dendritic cells, but cross-presented to CD8 T cells by CD8+ dendritic cells", J Immunol, 166, pp.5327~5330 (2001)
  53. Gerner MY, "Defective MHC class II presentation by dendritic cells limits CD4 T cell help for antitumor CD8 T cell responses", J Immunol, 181, pp.155~164 (2008)
  54. Joffre OP, "Cross-presentation by dendritic cells", Nat Rev Immunol, 12, pp.557~569 (2012)
  55. Alloatti A, "Dendritic cell maturation and cross-presentation:timing matters!", Immunol Rev, 272, pp.97~108 (2016)
  56. Embgenbroich M, "Current concepts of antigen cross-presentation", Front Immunol, 9, pp.1643~ (2018)
  57. Gros M, "Regulation of antigen export to the cytosol during cross-presentation", Front Immunol, 10, pp.41~ (2019)

관련 논문AI추천

Intranasal Vaccination with Outer-Membrane Protein of Orientia tsutsugamushi induces Protective Immunity Against Scrub Typhus주혁, 구민정, 길병철, 박성무, 손영민, 심병식, 윤철희, 정운희, 정항진, 주영준, 천인수, 최상호, 한승현, 황규잠대한면역학회 · Immune Network2021 · 제21권 제2호Protective Immunity of 56-kDa Type-Specific Antigen of Orientia tsutsugamushi Causing Scrub Typhus최상호, Byoungchul Gill, Hang-Jin Jeong, Jeongmin Lee, Kyu-Jam Hwang, Young Ran JU3한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2014 · 제24권 제12호Potentiation of Th1-Type Immune Responses to Mycobacterium tuberculosis Antigens in Mice by Cationic Liposomes Combined with De-O-Acylated Lipooligosaccharide고아라, 김광성, 류지인, 박신애, 신성재, 위서리, 이나경, 이연정, 이인무, 조양제, DO THI THU HIEN한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2018 · 제28권 제1호Oxidized Carbon Nanosphere-Based Subunit Vaccine Delivery System Elicited Robust Th1 and Cytotoxic T Cell ResponsesChutamath Sittplangkoo, Felipe Cia, Gregory J. Bancroft, Pritsana Sawutdeechaikul, Supason Wanichwecharungruang, Tanapat Palaga한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2019 · 제29권 제3호A Synthetic Tul4 and FopA Peptide Cocktail of Francisella tularensis Induces Humoral and Cell-Mediated Immune Responses in Mice김경설, Chang-Hwan Kim, Gyeunghaeng Hur, Hanseul Oh, Jae-Hak Park한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2016 · 제26권 제9호Nasal Immunization Using Chitosan Nanoparticles with Glycoprotein B of Murine CytomegalovirusBostik Pavel, Hatala Alexandra, Janovska Sylva, Mannova Nikola, Metelka Radovan, Pudelka Ludovit, Radochova Vera, Sleha Radek, Slovakova Marcela한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2024 · 제34권 제3호

이 간행물의 다른 논문 (5건)