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

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.

GRAPHICAL ABSTRACT

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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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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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KEY WORDS

  • PLGA nanospheres
  • chitosan
  • trimethyl chitosan
  • nasal delivery
  • mucosal and cell-mediated responses