Chitosan (CHT) and trimethylchitosan (TMC) nanoparticles as adjuvant/delivery system for parenteral and nasal immunization against Mycobacterium tuberculosis (MTb) ESAT-6 antigen

Document Type : Research Paper

Authors

1 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Faculty of Medicine and Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Antimicrobial Resistance Research Center, Department of Medical Bacteriology and Virology, Qaem University Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): An efficient vaccine against TB is an urgent need. TB peptides are safe candidate but they are weak immunogens and needs to be potentiated by adjuvant/delivery systems. The main purpose of the present study was to determine the potential of CHT based NPs containing ESAT-6 antigen of M. tuberculosis for inducing mucosal and systemic immune responses after intranasal and subcutaneous injection in mice model.
Materials and Methods: CHT and TMC based NPs were prepared by coating of cationic polymer on the anionic peptide by ionic gelation method and their characteristics were evaluated by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Physical stability of NPs was studied within 30 days. Finally, the ability of formulated NPs to elicit immune responses in BALB/c mice were evaluated following nasal and subcutaneous immunization.
Results: The best weight ratio of antigen to polymer (CHT or TMC) was 1:2. CHT and TMC NPs had a mean size of 356.3 ± 42.20, and 470.3 ± 48.21 nm, respectively. NPs were stable up to 15 days. CHT:ESAT-6 NPs gave higher serum IgG1 and IgG total responses and TMC:ESAT-6 NPs induced high titers of IgG2a and IFN-g.
Conclusion: Regards to the importance of cellular immune responses in effective protection against TB, and also the solubility in physiological pH, TMC NPs are more efficient adjuvant/antigen delivery system for immunization against TB.

Keywords

References

1. Ali IFA, Babak F, Fazlollah MS, Nematollah JJ. Rapid detection of MDR–Mycobacterium tuberculosis using modified PCR-SSCP from clinical Specimens. Asian Pac J Trop Biomed 2014; 4:165-170.
2. Tyagi AK, Nangpal P, Satchidanandam V. Development of vaccines against tuberculosis. Tuberculosis 2011; 91(5): 469-478.
3. Liu Y, Yin Y, Wang L, Zhang W, Chen X, Yang X, et al. Engineering biomaterial-associated complement activation to improve vaccine efficacy. Biomacromolecules 2013; 14(9): 3321-3328.
4. Olsen AW, van Pinxteren LA, Okkels LM, Rasmussen PB, Andersen P. Protection of mice with a tuberculosis subunit vaccine based on a fusion protein of antigen 85b and esat-6. Infect Immun 2001; 69(5): 2773-2778.
5. Olsen AW, Hansen PR, Holm A, Andersen P. Efficient protection against Mycobacterium tuberculosis by vaccination with a single subdominant epitope from the ESAT-6 antigen. Eur J Immunol 2000; 30(6): 1724-1732.
6. Ravn P, Demissie A, Eguale T, Wondwosson H, Lein D, Amoudy HA, et al. Human T cell responses to the ESAT-6 antigen from Mycobacterium tuberculosis. J Infec Dis 1999; 179(3): 637-645.
7. Demissie A, Leyten EM, Abebe M, Wassie L, Aseffa A, Abate G, et al. Recognition of stage-specific mycobacterial antigens differentiates between acute and latent infections with Mycobacterium tuberculosis. Clin Vaccine Immunol 2006; 13(2):179-186.
8. Cardoso FL, Antas PR, Milagres AS, Geluk A, Franken KL, Oliveira EB, et al. T-cell responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 in Brazilian tuberculosis patients. Infect Immun 2002; 70(12): 6707-6714.
9. Garg NK, Dwivedi P, Jain A, Tyagi S, Sahu T, Tyagi RK. Development of novel carrier (s) mediated tuberculosis vaccine: More than a tour de force. Eur J Pharm Sci 2014; 62: 227-242.
10. Islam MA, Firdous J, Choi Y-J, Yun C-H, Cho C-S. Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review. Int J Nanomedicine 2012; 7: 6077-6093.
11. Giri PK, Verma I, Khuller GK. Enhanced immunoprotective potential of Mycobacterium tuberculosis Ag85 complex protein based vaccine against airway Mycobacterium tuberculosis challenge following intranasal administration. FEMS Immunol Med Microbiol 2006; 47(2):233-241.
12. Tafaghodi M, Saluja V, Kersten GF, Kraan H, Slütter B, Amorij J-P, et al. Hepatitis B surface antigen nanoparticles coated with chitosan and trimethyl chitosan: Impact of formulation on physicochemical and immunological characteristics. Vaccine 2012; 30(36): 5341-5348.
13. Mustafa A, Oftung F, Amoudy H, Madi N, Abal A, Shaban F, et al. Multiple epitopes from the Mycobacterium tuberculosis ESAT-6 antigen are recognized by antigen-specific human T cell lines. Clin Infect Dis 2000; 30(3): S201-S5.
14. Gregory AE, Titball R, Williamson D. Vaccine delivery using nanoparticles. Front Cell Infect Microbiol 2013; 3(13): 1-13.
15. Mohaghegh M, Tafaghodi M. Dextran microspheres could enhance immune responses against PLGA nanospheres encapsulated with tetanus toxoid and Quillaja saponins after nasal immunization in rabbit. Pharm Dev Technol. 2011; 16(1): 36-43.
16. Tafaghodi M, Rastegar S. Preparation and in vivo study of dry powder microspheres for nasal immunization. J Drug Target 2010; 18(3): 235-242.
17. Tafaghodi M, Khamesipour A, Jaafari M. Immunization against leishmaniasis by PLGA nanospheres loaded with an experimental Autoclaved Leishmania major (ALM) and Quillajasaponins. Trop Biomed 2010; 27(3): 639-650.
18. Chen WR. Chitin, chitosan, and glycated chitosan regulate immune responses: the novel adjuvants for cancer vaccine. Clin Dev Immunol 2013; 2013:1-8.
19. 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): 107-116.
20. Boontha S, Junginger HE, Waranuch N, Polnok A, Pitaksuteepong T. Chitosan and trimethyl chitosan particles as oral vaccine delivery systems: comparison of the potential to initiate immune responses. Journal of Metals, Materials and Minerals 2011; 21(1): 43-47.
21. Seferian PG, Martinez ML. Immune stimulating activity of two new chitosan containing adjuvant formulations. Vaccine 2000; 19(6): 661-668.
22. Zaharoff DA, Rogers CJ, Hance KW, Schlom J, Greiner JW. Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination. Vaccine 2007; 25(11): 2085-2094.
23. Jabbal-Gill I, Fisher AN, Rappel R, Davis SS, Illum L. Stimulation of mucosal and systemic antibody responses against Bordetella pertussis filamentous haemagglutinin and recombinant pertussis toxin after nasal administration with chitosan in mice. Vaccine 1998; 16(20): 2039-2046.
Nanomedicine Journal
Volume 3, Issue 4
October 2016
Pages 223-229

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