Enhancing immunogenicity of novel multistage subunit vaccine of Mycobacterium tuberculosis using PLGA:DDA hybrid nanoparticles and MPLA : subcutaneous administration

Objective(s): A new strategy in recent studies is using effective tuberculosis (TB) subunit vaccines combined with appropriate carriers and adjuvants which have shown promising results in preclinical and clinical studies. The aim of the present study was to evaluate the PLGA:DDA hybrid nanoparticles...

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Main Authors: Farzad Khademi, Arshid Yousefi, Mohammad Derakhshan, Adel Najafi, Mohsen Tafaghodi
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2019-08-01
Series:Iranian Journal of Basic Medical Sciences
Subjects:
Online Access:http://ijbms.mums.ac.ir/article_13321_066c72f5407dd8f47bd090c7d1a9a493.pdf
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author Farzad Khademi
Arshid Yousefi
Mohammad Derakhshan
Adel Najafi
Mohsen Tafaghodi
author_facet Farzad Khademi
Arshid Yousefi
Mohammad Derakhshan
Adel Najafi
Mohsen Tafaghodi
author_sort Farzad Khademi
collection DOAJ
description Objective(s): A new strategy in recent studies is using effective tuberculosis (TB) subunit vaccines combined with appropriate carriers and adjuvants which have shown promising results in preclinical and clinical studies. The aim of the present study was to evaluate the PLGA:DDA hybrid nanoparticles (NPs) for subcutaneous delivery of a novel multistage subunit vaccine along with MPLA adjuvant against Mycobacterium tuberculosis (M. tuberculosis). Materials and Methods: PLGA and PLGA:DDA NPs containing HspX/EsxS fusion protein and MPLA were prepared by double emulsion method (w/o/w). After characterization, these NPs were subcutaneously administered to BALB/c mice aged 6-8 weeks old. Immunogenicity of formulations were assessed by measuring the level of IFN-γ, IL-4, IL-17 and TGF-β cytokines as well as IgG1, IgG2a and IgA antibodies using ELISA. Results: Both particles had spherical shape and smooth surface with 316.7 ± 12.7 nm in size, surface charge of -33 ± 1.7 mV, and encapsulation efficiency of 92.2 ± 2% for PLGA NPs and 249.7 ± 16.7 nm in size, surface charge of 39 ± 1.8 mV, and encapsulation efficiency of 35.7 ± 1.4% for PLGA:DDA NPs. The highest IFN-γ response and also IgG2a and IgG1 antibodies titers were observed in groups immunized with PLGA:DDA/HspX/EsxS/MPLA and PLGA:DDA/HspX/EsxS/MPLA as booster as well as PLGA:DDA/HspX/EsxS and PLGA:DDA/HspX/EsxS as booster. Conclusion: With regard to effective induction of IFN-γ and IgG2a immune responses, PLGA:DDA hybrid NP along with MPLA adjuvant have good potentials for improving the immunogenicity of HspX/EsxS multistage subunit vaccine as well as promoting BCG efficacy as a BCG prime-boost.
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spelling doaj.art-1a5def8921bc4f86b6494badb76c40222022-12-21T19:10:31ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742019-08-0122889390010.22038/ijbms.2019.33962.807913321Enhancing immunogenicity of novel multistage subunit vaccine of Mycobacterium tuberculosis using PLGA:DDA hybrid nanoparticles and MPLA : subcutaneous administrationFarzad Khademi0Arshid Yousefi1Mohammad Derakhshan2Adel Najafi3Mohsen Tafaghodi4Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, IranDepartment of Medical Bacteriology and Virology, Qaem University Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Medical Bacteriology and Virology, Qaem University Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Medical Bacteriology and Virology, Qaem University Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IranNanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran|Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranObjective(s): A new strategy in recent studies is using effective tuberculosis (TB) subunit vaccines combined with appropriate carriers and adjuvants which have shown promising results in preclinical and clinical studies. The aim of the present study was to evaluate the PLGA:DDA hybrid nanoparticles (NPs) for subcutaneous delivery of a novel multistage subunit vaccine along with MPLA adjuvant against Mycobacterium tuberculosis (M. tuberculosis). Materials and Methods: PLGA and PLGA:DDA NPs containing HspX/EsxS fusion protein and MPLA were prepared by double emulsion method (w/o/w). After characterization, these NPs were subcutaneously administered to BALB/c mice aged 6-8 weeks old. Immunogenicity of formulations were assessed by measuring the level of IFN-γ, IL-4, IL-17 and TGF-β cytokines as well as IgG1, IgG2a and IgA antibodies using ELISA. Results: Both particles had spherical shape and smooth surface with 316.7 ± 12.7 nm in size, surface charge of -33 ± 1.7 mV, and encapsulation efficiency of 92.2 ± 2% for PLGA NPs and 249.7 ± 16.7 nm in size, surface charge of 39 ± 1.8 mV, and encapsulation efficiency of 35.7 ± 1.4% for PLGA:DDA NPs. The highest IFN-γ response and also IgG2a and IgG1 antibodies titers were observed in groups immunized with PLGA:DDA/HspX/EsxS/MPLA and PLGA:DDA/HspX/EsxS/MPLA as booster as well as PLGA:DDA/HspX/EsxS and PLGA:DDA/HspX/EsxS as booster. Conclusion: With regard to effective induction of IFN-γ and IgG2a immune responses, PLGA:DDA hybrid NP along with MPLA adjuvant have good potentials for improving the immunogenicity of HspX/EsxS multistage subunit vaccine as well as promoting BCG efficacy as a BCG prime-boost.http://ijbms.mums.ac.ir/article_13321_066c72f5407dd8f47bd090c7d1a9a493.pdfMycobacterium tuberculosisMultistage subunit vaccinePLGA:DDA nanoparticleMPLAImmunization
spellingShingle Farzad Khademi
Arshid Yousefi
Mohammad Derakhshan
Adel Najafi
Mohsen Tafaghodi
Enhancing immunogenicity of novel multistage subunit vaccine of Mycobacterium tuberculosis using PLGA:DDA hybrid nanoparticles and MPLA : subcutaneous administration
Iranian Journal of Basic Medical Sciences
Mycobacterium tuberculosis
Multistage subunit vaccine
PLGA:DDA nanoparticle
MPLA
Immunization
title Enhancing immunogenicity of novel multistage subunit vaccine of Mycobacterium tuberculosis using PLGA:DDA hybrid nanoparticles and MPLA : subcutaneous administration
title_full Enhancing immunogenicity of novel multistage subunit vaccine of Mycobacterium tuberculosis using PLGA:DDA hybrid nanoparticles and MPLA : subcutaneous administration
title_fullStr Enhancing immunogenicity of novel multistage subunit vaccine of Mycobacterium tuberculosis using PLGA:DDA hybrid nanoparticles and MPLA : subcutaneous administration
title_full_unstemmed Enhancing immunogenicity of novel multistage subunit vaccine of Mycobacterium tuberculosis using PLGA:DDA hybrid nanoparticles and MPLA : subcutaneous administration
title_short Enhancing immunogenicity of novel multistage subunit vaccine of Mycobacterium tuberculosis using PLGA:DDA hybrid nanoparticles and MPLA : subcutaneous administration
title_sort enhancing immunogenicity of novel multistage subunit vaccine of mycobacterium tuberculosis using plga dda hybrid nanoparticles and mpla subcutaneous administration
topic Mycobacterium tuberculosis
Multistage subunit vaccine
PLGA:DDA nanoparticle
MPLA
Immunization
url http://ijbms.mums.ac.ir/article_13321_066c72f5407dd8f47bd090c7d1a9a493.pdf
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