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Immunological Assessment of Chitosan or Trimethyl Chitosan-Coated PLGA Nanospheres Containing Fusion Antigen as the Novel Vaccine Candidates Against Tuberculosis

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Abstract

The crucial challenge in tuberculosis (TB) as a chronic infectious disease is to present a novel vaccine candidate that improves current vaccination and provides efficient protection in individuals. The present study aimed to evaluate the immune efficacy of multi-subunit vaccines containing chitosan (CHT)- or trimethyl chitosan (TMC)-coated PLGA nanospheres to stimulate cell-mediated and mucosal responses against Mycobacterium Tuberculosis (Mtb) in an animal model. The surface-modified PLGA nanoparticles (NPs) containing tri-fusion protein from three Mtb antigens were produced by the double emulsion technique. The subcutaneously or nasally administered PLGA vaccines in the absence or presence of BCG were assessed to compare the levels of mucosal IgA, IgG1, and IgG2a production as well as secretion of IFN-γ, IL-17, IL-4, and TGF-β cytokines. According to the release profile, the tri-fusion encapsulated in modified PLGA NPs demonstrated a biphasic release profile including initial burst release on the first day and sustained release within 18 days. All designed PLGA vaccines induced a shift of Th1/Th2 balance toward Th1-dominant response. Although immunized mice through subcutaneous injection elicited higher cell-mediated responses relative to the nasal vaccination, the intranasally administered groups stimulated robust mucosal IgA immunity. The modified PLGA NPs using TMC cationic polymer were more efficient to elevate Th1 and mucosal responses in comparison with the CHT-coated PLGA nanospheres. Our findings highlighted that the tri-fusion loaded in TMC-PLGA NPs may represent an efficient prophylactic vaccine and can be considered as a novel candidate against TB.

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References

  1. Chen X, Wang K, Li H, Hong L, He J. Current status and progress of specific laboratory examination methods of active tuberculosis infection diagnosis. Nano Biomed Eng. 2018;10(1):79–86.

    Article  Google Scholar 

  2. Herbert N, Sharma V, Masham BS, Sheehan BS, Hauser J, Zumla A. Concrete action now: UN high-level meeting on tuberculosis. Lancet Infect Dis. 2018.

  3. Kaufmann SH, Lange C, Rao M, Balaji KN, Lotze M, Schito M, et al. Progress in tuberculosis vaccine development and host-directed therapies—a state of the art review. Lancet Respir Med. 2014;2(4):301–20.

    Article  CAS  PubMed  Google Scholar 

  4. Andersen P. TB vaccines: progress and problems. Trends Immunol. 2001;22(3):160–8.

    Article  CAS  PubMed  Google Scholar 

  5. Babiuk LA. Broadening the approaches to developing more effective vaccines. Vaccine. 1999;17(13–14):1587–95.

    Article  CAS  PubMed  Google Scholar 

  6. Martin C, Aguilo N, Marinova D, Gonzalo-Asensio J. Update on TB vaccine pipeline. Appl Sci. 2020;10(7):2632.

    Article  CAS  Google Scholar 

  7. Arregui S, Sanz J, Marinova D, Martín C, Moreno Y. On the impact of masking and blocking hypotheses for measuring the efficacy of new tuberculosis vaccines. PeerJ. 2016;4:e1513.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Andersen P, Kaufmann SH. Novel vaccination strategies against tuberculosis. Cold Spring Harb Perspect Med. 2014;4(6):a018523.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Marinova D, Gonzalo-Asensio J, Aguilo N, Martin C. MTBVAC from discovery to clinical trials in tuberculosis-endemic countries. Expert Rev Vaccines. 2017;16(6):565–76.

    Article  CAS  PubMed  Google Scholar 

  10. Sable SB, Posey JE, Scriba TJ. Tuberculosis vaccine development: progress in clinical evaluation. Clin Microbiol Rev. 2019;33(1).

  11. Annabel B, Anna D, Hannah M. Global tuberculosis report 2019. Geneva: WHO; 2019.

    Google Scholar 

  12. Smaill F, Jeyanathan M, Smieja M, Medina MF, Thanthrige-Don N, Zganiacz A, et al. A human type 5 adenovirus–based tuberculosis vaccine induces robust T cell responses in humans despite preexisting anti-adenovirus immunity. Sci Transl Med. 2013;5(205):205ra134.

    Article  PubMed  Google Scholar 

  13. Van Der Meeren O, Hatherill M, Nduba V, Wilkinson RJ, Muyoyeta M, Van Brakel E, et al. Phase 2b controlled trial of M72/AS01E vaccine to prevent tuberculosis. N Engl J Med. 2018;379(17):1621–34.

    Article  Google Scholar 

  14. Tait DR, Hatherill M, Van Der Meeren O, Ginsberg AM, Van Brakel E, Salaun B, et al. Final analysis of a trial of M72/AS01E vaccine to prevent tuberculosis. N Engl J Med. 2019;381(25):2429–39.

    Article  CAS  PubMed  Google Scholar 

  15. Coler RN, Day TA, Ellis R, Piazza FM, Beckmann AM, Vergara J, et al. The TLR-4 agonist adjuvant, GLA-SE, improves magnitude and quality of immune responses elicited by the ID93 tuberculosis vaccine: first-in-human trial. NPJ Vaccines. 2018;3(1):1–9.

    Article  CAS  Google Scholar 

  16. Penn-Nicholson A, Tameris M, Smit E, Day TA, Musvosvi M, Jayashankar L, et al. Safety and immunogenicity of the novel tuberculosis vaccine ID93+ GLA-SE in BCG-vaccinated healthy adults in South Africa: a randomised, double-blind, placebo-controlled phase 1 trial. Lancet Respir Med. 2018;6(4):287–98.

    Article  CAS  PubMed  Google Scholar 

  17. Hoang T, Aagaard C, Dietrich J, Cassidy JP, Dolganov G, Schoolnik GK, et al. ESAT-6 (EsxA) and TB10. 4 (EsxH) based vaccines for pre-and post-exposure tuberculosis vaccination. PLoS One. 2013;8(12):e80579.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Moradi B, Sankian M, Amini Y, Meshkat Z. Construction of a novel DNA vaccine candidate encoding an HspX-PPE44-EsxV fusion antigen of mycobacterium tuberculosis. Rep Biochem Mol Biol. 2016;4(2):89.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Amini Y, Moradi B, Tafaghodi M, Meshkat Z, Ghazvini K, Fasihi-Ramandi M. TB trifusion antigen adsorbed on calcium phosphate nanoparticles stimulates strong cellular immunity in mice. Biotechnol Bioprocess Eng. 2016;21(5):653–8.

    Article  CAS  Google Scholar 

  20. Achkar JM, Chan J, Casadevall A. B cells and antibodies in the defense against Mycobacterium tuberculosis infection. Immunol Rev. 2015;264(1):167–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jasenosky LD, Scriba TJ, Hanekom WA, Goldfeld AE. T cells and adaptive immunity to Mycobacterium tuberculosis in humans. Immunol Rev. 2015;264(1):74–87.

    Article  CAS  PubMed  Google Scholar 

  22. Sefidi-Heris Y, Jahangiri A, Mokhtarzadeh A, Shahbazi M-A, Khalili S, Baradaran B, et al. Recent progress in the design of DNA vaccines against tuberculosis. Drug Discov Today. 2020.

  23. Garg KN, Mangal S, Khambete H, Sharma KP, Tyagi RK. Mucosal delivery of vaccines: role of mucoadhesive/biodegradable polymers. Recent Pat Drug Deliv Formul. 2010;4(2):114–28.

    Article  CAS  PubMed  Google Scholar 

  24. Pati R, Shevtsov M, Sonawane A. Nanoparticle vaccines against infectious diseases. Front Immunol. 2018;9:2224.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Mosafer J, Abnous K, Tafaghodi M, Jafarzadeh H, Ramezani M. Preparation and characterization of uniform-sized PLGA nanospheres encapsulated with oleic acid-coated magnetic-Fe3O4 nanoparticles for simultaneous diagnostic and therapeutic applications. Colloids Surf A Physicochem Eng Asp. 2017;514:146–54.

    Article  CAS  Google Scholar 

  26. Jaganathan K, Vyas SP. Strong systemic and mucosal immune responses to surface-modified PLGA microspheres containing recombinant hepatitis B antigen administered intranasally. Vaccine. 2006;24(19):4201–11.

    Article  CAS  PubMed  Google Scholar 

  27. Kabiri M, Sankian M, Sadri K, Tafaghodi M. Robust mucosal and systemic responses against HTLV-1 by delivery of multi-epitope vaccine in PLGA nanoparticles. Eur J Pharm Biopharm. 2018;133:321–30.

    Article  CAS  PubMed  Google Scholar 

  28. Du G, Hathout RM, Nasr M, Nejadnik MR, Tu J, Koning RI, et al. Intradermal vaccination with hollow microneedles: a comparative study of various protein antigen and adjuvant encapsulated nanoparticles. J Control Release. 2017;266:109–18.

    Article  CAS  PubMed  Google Scholar 

  29. Perez C, Sanchez A, Putnam D, Ting D, Langer R, Alonso M. Poly (lactic acid)-poly (ethylene glycol) nanoparticles as new carriers for the delivery of plasmid DNA. J Control Release. 2001;75(1–2):211–24.

    Article  CAS  PubMed  Google Scholar 

  30. Chaturvedi M, Kumar M, Pathak K. A review on mucoadhesive polymer used in nasal drug delivery system. J Adv Pharm Technol Res. 2011;2(4):215–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Amidi M, Romeijn SG, Borchard G, Junginger HE, Hennink WE, Jiskoot W. Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system. J Control Release. 2006;111(1):107–16.

    Article  CAS  PubMed  Google Scholar 

  32. Csaba N, Garcia-Fuentes M, Alonso MJ. Nanoparticles for nasal vaccination. Adv Drug Deliv Rev. 2009;61(2):140–57.

    Article  CAS  PubMed  Google Scholar 

  33. Wang Y, Li P, Kong L. Chitosan-modified PLGA nanoparticles with versatile surface for improved drug delivery. AAPS PharmSciTech. 2013;14(2):585–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kabiri M, Bolourian H, Dehghan S, Tafaghodi M. The dry powder formulation of mixed cross-linked dextran microspheres and tetanus toxoid-loaded trimethyl chitosan nanospheres as a potent adjuvant for nasal delivery system. Iran J Basic Med Sci. 2020;24(1):116–22.

    Google Scholar 

  35. Dehghan S, Kheiri MT, Tabatabaiean M, Darzi S, Tafaghodi M. Dry-powder form of chitosan nanospheres containing influenza virus and adjuvants for nasal immunization. Arch Pharm Res. 2013;36(8):981–92.

    Article  CAS  PubMed  Google Scholar 

  36. Slütter B, Bal S, Keijzer C, Mallants R, Hagenaars N, Que I, et al. Nasal vaccination with N-trimethyl chitosan and PLGA based nanoparticles: nanoparticle characteristics determine quality and strength of the antibody response in mice against the encapsulated antigen. Vaccine. 2010;28(38):6282–91.

    Article  PubMed  Google Scholar 

  37. Hamman J, Kotze A. Effect of the type of base and number of reaction steps on the degree of quaternization and molecular weight of N-trimethyl chitosan chloride. Drug Dev Ind Pharm. 2001;27(5):373–80.

    Article  CAS  PubMed  Google Scholar 

  38. Bal SM, Slütter B, van Riet E, Kruithof AC, Ding Z, Kersten GF, et al. Efficient induction of immune responses through intradermal vaccination with N-trimethyl chitosan containing antigen formulations. J Control Release. 2010;142(3):374–83.

    Article  CAS  PubMed  Google Scholar 

  39. Amini Y, AmelJamehdar S, Sadri K, Zare S, Musavi D, Tafaghodi M. Different methods to determine the encapsulation efficiency of protein in PLGA nanoparticles. Biomed Mater Eng. 2017;28(6):613–20.

    CAS  PubMed  Google Scholar 

  40. Frey A, Di Canzio J, Zurakowski D. A statistically defined endpoint titer determination method for immunoassays. J Immunol Methods. 1998;221(1–2):35–41.

    Article  CAS  PubMed  Google Scholar 

  41. Andersen P, Scriba TJ. Moving tuberculosis vaccines from theory to practice. Nat Rev. 2019;19(9):550–62.

    CAS  Google Scholar 

  42. Khademi F, Derakhshan M, Yousefi-Avarvand A, Tafaghodi M, Soleimanpour S. Multi-stage subunit vaccines against Mycobacterium tuberculosis: an alternative to the BCG vaccine or a BCG-prime boost? Expert Rev Vaccines. 2018;17(1):31–44.

    Article  CAS  PubMed  Google Scholar 

  43. Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, et al. Efficacy of BCG vaccine in the prevention of tuberculosis: meta-analysis of the published literature. JAMA. 1994;271(9):698–702.

    Article  CAS  PubMed  Google Scholar 

  44. Niu H, Peng J, Bai C, Liu X, Hu L, Luo Y, et al. Multi-stage tuberculosis subunit vaccine candidate LT69 provides high protection against Mycobacterium tuberculosis infection in mice. PLoS One. 2015;10(6):e0130641.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Xin Q, Niu H, Li Z, Zhang G, Hu L, Wang B, et al. Subunit vaccine consisting of multi-stage antigens has high protective efficacy against Mycobacterium tuberculosis infection in mice. PLoS One. 2013;8(8):e72745.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bertholet S, Ireton GC, Kahn M, Guderian J, Mohamath R, Stride N, et al. Identification of human T cell antigens for the development of vaccines against Mycobacterium tuberculosis. J Immunol. 2008;181(11):7948–57.

    Article  CAS  PubMed  Google Scholar 

  47. Knudsen NPH, Nørskov-Lauritsen S, Dolganov GM, Schoolnik GK, Lindenstrøm T, Andersen P, et al. Tuberculosis vaccine with high predicted population coverage and compatibility with modern diagnostics. Proc Natl Acad Sci. 2014;111(3):1096–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Bonanni D, Rindi L, Lari N, Garzelli C. Immunogenicity of mycobacterial PPE44 (Rv2770c) in Mycobacterium bovis BCG-infected mice. J Med Microbiol. 2005;54(Pt 5):443–8.

    Article  CAS  PubMed  Google Scholar 

  49. Zumla A, Malon P, Henderson J, Grange JM. Impact of HIV infection on tuberculosis. Postgrad Med J. 2000;76(895):259–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kabiri M, Sankian M, Hosseinpour M, Tafaghodi M. The novel immunogenic chimeric peptide vaccine to elicit potent cellular and mucosal immune responses against HTLV-1. Int J Pharm. 2018;549(1–2):404–14.

    Article  CAS  PubMed  Google Scholar 

  51. Demento SL, Cui W, Criscione JM, Stern E, Tulipan J, Kaech SM, et al. Role of sustained antigen release from nanoparticle vaccines in shaping the T cell memory phenotype. Biomaterials. 2012;33(19):4957–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Scheerlinck J-PY, Greenwood DL. Virus-sized vaccine delivery systems. Drug Discov Today. 2008;13(19–20):882–7.

    Article  CAS  PubMed  Google Scholar 

  53. Foged C, Brodin B, Frokjaer S, Sundblad A. Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model. Int J Pharm. 2005;298(2):315–22.

    Article  CAS  PubMed  Google Scholar 

  54. Pawar D, Mangal S, Goswami R, Jaganathan KS. Development and characterization of surface modified PLGA nanoparticles for nasal vaccine delivery: effect of mucoadhesive coating on antigen uptake and immune adjuvant activity. Eur J Pharm Biopharm. 2013;85(3, Part A):550–9.

    Article  CAS  PubMed  Google Scholar 

  55. Dehghan S, Tafaghodi M, Bolourieh T, Mazaheri V, Torabi A, Abnous K, et al. Rabbit nasal immunization against influenza by dry-powder form of chitosan nanospheres encapsulated with influenza whole virus and adjuvants. Int J Pharm. 2014;475(1–2):1–8.

    Article  CAS  PubMed  Google Scholar 

  56. Wang JJ, Zeng ZW, Xiao RZ, Xie T, Zhou GL, Zhan XR, et al. Recent advances of chitosan nanoparticles as drug carriers. Int J Nanomedicine. 2011;6:765.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Sayın B, Somavarapu S, Li X, Thanou M, Sesardic D, Alpar H, et al. Mono-N-carboxymethyl chitosan (MCC) and N-trimethyl chitosan (TMC) nanoparticles for non-invasive vaccine delivery. Int J Pharm. 2008;363(1–2):139–48.

    Article  PubMed  Google Scholar 

  58. Zhao J, Li J, Jiang Z, Tong R, Duan X, Bai L, et al. Chitosan, N, N, N-trimethyl chitosan (TMC) and 2-hydroxypropyltrimethyl ammonium chloride chitosan (HTCC): the potential immune adjuvants and nano carriers. Int J Biol Macromol. 2020.

  59. Kaushal D, Foreman TW, Gautam US, Alvarez X, Adekambi T, Rangel-Moreno J, et al. Mucosal vaccination with attenuated Mycobacterium tuberculosis induces strong central memory responses and protects against tuberculosis. Nat Commun. 2015;6(1):1–14.

    Article  Google Scholar 

  60. Dijkman K, Sombroek CC, Vervenne RA, Hofman SO, Boot C, Remarque EJ, et al. Prevention of tuberculosis infection and disease by local BCG in repeatedly exposed rhesus macaques. Nat Med. 2019;25(2):255–62.

    Article  CAS  PubMed  Google Scholar 

  61. Woodworth JS, Cohen SB, Moguche AO, Plumlee CR, Agger EM, Urdahl KB, et al. Subunit vaccine H56/CAF01 induces a population of circulating CD4 T cells that traffic into the Mycobacterium tuberculosis-infected lung. Mucosal Immunol. 2017;10(2):555–64.

    Article  CAS  PubMed  Google Scholar 

  62. Ahmed M, Smith DM, Hamouda T, Rangel-Moreno J, Fattom A, Khader SA. A novel nanoemulsion vaccine induces mucosal Interleukin-17 responses and confers protection upon Mycobacterium tuberculosis challenge in mice. Vaccine. 2017;35(37):4983–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Li M, Zhao M, Fu Y, Li Y, Gong T, Zhang Z, et al. Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra-and paracellular pathways. J Control Release. 2016;228:9–19.

    Article  CAS  PubMed  Google Scholar 

  64. Mai Y, Guo J, Zhao Y, Ma S, Hou Y, Yang J. Intranasal delivery of cationic liposome-protamine complex mRNA vaccine elicits effective anti-tumor immunity. Cell Immunol. 2020:104143.

  65. Lycke N. Recent progress in mucosal vaccine development: potential and limitations. Nat Rev. 2012;12(8):592–605.

    CAS  Google Scholar 

  66. Wilson HL, Gerdts V, Babiuk LA. Mucosal vaccine development for veterinary and aquatic diseases. Mucosal vaccines. Elsevier; 2020. p. 811–29.

    Google Scholar 

  67. Torrado E, Cooper AM. IL-17 and Th17 cells in tuberculosis. Cytokine Growth Factor Rev. 2010;21(6):455–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Cruz A, Fraga AG, Fountain JJ, Rangel-Moreno J, Torrado E, Saraiva M, et al. Pathological role of interleukin 17 in mice subjected to repeated BCG vaccination after infection with Mycobacterium tuberculosis. J Exp Med. 2010;207(8):1609–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Nembrini C, Marsland BJ, Kopf M. IL-17–producing T cells in lung immunity and inflammation. J Allergy Clin Immunol. 2009;123(5):986–94.

    Article  CAS  PubMed  Google Scholar 

  70. Khader SA, Cooper AM. IL-23 and IL-17 in tuberculosis. Cytokine. 2008;41(2):79–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Whitlow E, Mustafa A, Hanif S. An overview of the development of new vaccines for tuberculosis. Vaccines. 2020;8(4):586.

    Article  CAS  PubMed Central  Google Scholar 

  72. Hu S, He W, Du X, Yang J, Wen Q, Zhong X-P, et al. IL-17 Production of neutrophils enhances antibacteria ability but promotes arthritis development during Mycobacterium tuberculosis infection. EBioMedicine. 2017;23:88–99.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Trentini MM, de Oliveira FM, Kipnis A, Junqueira-Kipnis AP. The role of neutrophils in the induction of specific Th1 and Th17 during vaccination against tuberculosis. Front Microbiol. 2016;7:898.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Khader SA, Bell GK, Pearl JE, Fountain JJ, Rangel-Moreno J, Cilley GE, et al. IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol. 2007;8(4):369–77.

    Article  CAS  PubMed  Google Scholar 

  75. Umemura M, Yahagi A, Hamada S, Begum MD, Watanabe H, Kawakami K, et al. IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection. J Immunol. 2007;178(6):3786–96.

    Article  CAS  PubMed  Google Scholar 

  76. Junqueira-Kipnis AP, De Oliveira FM, Trentini MM, Tiwari S, Chen B, Resende DP, et al. Prime–boost with Mycobacterium smegmatis recombinant vaccine improves protection in mice infected with Mycobacterium tuberculosis. PLoS One. 2013;8(11):e78639.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. da Costa AC, de Oliveira Costa-Junior A, de Oliveira FM, Nogueira SV, Rosa JD, Resende DP, et al. A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis. PLoS One. 2014;9(11):e112848.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Monin L, Griffiths K, Slight S, Lin Y-Y, Rangel-Moreno J, Khader SA. Immune requirements for protective Th17 recall responses to Mycobacterium tuberculosis challenge. Mucosal Immunol. 2015;8(5):1099–109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Lee Y-J, Han Y, Lu H-T, Nguyen V, Qin H, Howe PH, et al. TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression. J Immunol. 1997;158(5):2065–75.

    Article  CAS  PubMed  Google Scholar 

  80. Sasindran SJ, Torrelles JB. Mycobacterium tuberculosis infection and inflammation: what is beneficial for the host and for the bacterium? Front Microbiol. 2011;2:2.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Reed SG. TGF-β in infections and infectious diseases. Microb Infect. 1999;1(15):1313–25.

    Article  CAS  Google Scholar 

  82. Etna MP, Giacomini E, Severa M, Coccia EM, editors. Pro-and anti-inflammatory cytokines in tuberculosis: a two-edged sword in TB pathogenesis. Seminars in immunology. Elsevier; 2014.

  83. Hirsch CS, Yoneda T, Averill L, Ellner JJ, Toossi Z. Enhancement of intracellular growth of mycobacterium tuberculosis in human monocytes by transforming growth factor-βl. J Infect Dis. 1994;170(5):1229–37.

    Article  CAS  PubMed  Google Scholar 

  84. Hirsch CS, Ellner JJ, Blinkhorn R, Toossi Z. In vitro restoration of T cell responses in tuberculosis and augmentation of monocyte effector function against Mycobacterium tuberculosis by natural inhibitors of transforming growth factor β. Proc Natl Acad Sci. 1997;94(8):3926–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Toossi Z, Gogate P, Shiratsuchi H, Young T, Ellner JJ. Enhanced production of TGF-beta by blood monocytes from patients with active tuberculosis and presence of TGF-beta in tuberculous granulomatous lung lesions. J Immunol. 1995;154(1):465–73.

    Article  CAS  PubMed  Google Scholar 

  86. Michelson S, Alcami J, Kim S, Danielpour D, Bachelerie F, Picard L, et al. Human cytomegalovirus infection induces transcription and secretion of transforming growth factor beta 1. J Virol. 1994;68(9):5730–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Bhowmick S, Mazumdar T, Ali N. Vaccination route that induces transforming growth factor β production fails to elicit protective immunity against Leishmania donovani infection. Infect Immun. 2009;77(4):1514–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Yang L, Pang Y, Moses HL. TGF-β and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol. 2010;31(6):220–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to appreciate the Clinical Research Development Unit, Ghaem Hospital, Mashhad University of Medical Sciences for assisting in the data analysis.

Funding

The present study was financially supported by Mashhad University of Medical Sciences, Mashhad, Iran [grant number 941041].

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Author notes

  1. Sirwan Zare and Mona Kabiri contributed equally to this work.

Authors and Affiliations

  1. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Sirwan Zare & Seyed Hasan Ayati

  2. Clinical Research Development Unit, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

    Mona Kabiri

  3. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Mona Kabiri, Fatemeh Mohammadpour & Mohsen Tafaghodi

  4. Department of Microbiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

    Yousef Amini

  5. Clinical Microbiology Laboratory, Fatemieh Hospital, Hamedan University of Medical Sciences, Hamedan, Iran

    Adel Najafi

  6. Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

    Amin Reza Nikpoor

  7. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohsen Tafaghodi

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Contributions

S.Z., Y.A., A.N., F.M., S.H.A., and A.R.N. performed experiments and animal studies. S.Z. carried out the data collection. M.K. accomplished the statistical analysis of data and wrote the manuscript under the consultation of M.T. M.T. edited the manuscript as the supervisor and project administrator. All authors have read and approved the manuscript.

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Correspondence to Mohsen Tafaghodi.

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Zare, S., Kabiri, M., Amini, Y. et al. Immunological Assessment of Chitosan or Trimethyl Chitosan-Coated PLGA Nanospheres Containing Fusion Antigen as the Novel Vaccine Candidates Against Tuberculosis. AAPS PharmSciTech 23, 15 (2022). https://doi.org/10.1208/s12249-021-02146-z

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