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Nano-Encapsulated Melatonin: A Promising Mucosal Adjuvant in Intranasal Immunization against Chronic Experimental T. gondii Infection

Melatonin (MLT) is now emerging as one of the universally accepted immunostimulators with broad applications in medicine. It is a biological manipulator of the immune system, including mucosal ones. MLT was encapsulated in solid lipid nanoparticles (SLNs), then 100 mg/kg/dose of MLT-SLNs was used as...

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Autores principales: Said, Doaa E., Amer, Eglal I., Sheta, Eman, Makled, Shaimaa, Diab, Hala E., Arafa, Fadwa M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785012/
https://www.ncbi.nlm.nih.gov/pubmed/36548656
http://dx.doi.org/10.3390/tropicalmed7120401
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author Said, Doaa E.
Amer, Eglal I.
Sheta, Eman
Makled, Shaimaa
Diab, Hala E.
Arafa, Fadwa M.
author_facet Said, Doaa E.
Amer, Eglal I.
Sheta, Eman
Makled, Shaimaa
Diab, Hala E.
Arafa, Fadwa M.
author_sort Said, Doaa E.
collection PubMed
description Melatonin (MLT) is now emerging as one of the universally accepted immunostimulators with broad applications in medicine. It is a biological manipulator of the immune system, including mucosal ones. MLT was encapsulated in solid lipid nanoparticles (SLNs), then 100 mg/kg/dose of MLT-SLNs was used as an adjuvant of Toxoplasma lysate antigen (TLA). Experimental mice were intra-nasally inoculated with three doses of different regimens every two weeks, then challenged with 20 cysts of T. gondii Me49 strain, where they were sacrificed four weeks post-infection. Protective vaccine efficacy was evident via the significant brain cyst count reduction of 58.6%, together with remarkably high levels of humoral systemic and mucosal anti-Toxoplasma antibodies (Ig G, Ig A), supported by a reduced tachyzoites invasion of Vero cells in vitro upon incubation with sera obtained from these vaccinated mice. A cellular immune response was evident through the induction of significant levels of interferon-gamma (IFN γ), associated with morphological deteriorations of cysts harvested from the brains of vaccinated mice. Furthermore, the amelioration of infection-induced oxidative stress (OS) and histopathological changes were evident in mice immunized with TLA/MLT-SLNs. In conclusion, the present study highlighted the promising role of intranasal MLT-SLNs as a novel mucosal adjuvant candidate against chronic toxoplasmosis.
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spelling pubmed-97850122022-12-24 Nano-Encapsulated Melatonin: A Promising Mucosal Adjuvant in Intranasal Immunization against Chronic Experimental T. gondii Infection Said, Doaa E. Amer, Eglal I. Sheta, Eman Makled, Shaimaa Diab, Hala E. Arafa, Fadwa M. Trop Med Infect Dis Article Melatonin (MLT) is now emerging as one of the universally accepted immunostimulators with broad applications in medicine. It is a biological manipulator of the immune system, including mucosal ones. MLT was encapsulated in solid lipid nanoparticles (SLNs), then 100 mg/kg/dose of MLT-SLNs was used as an adjuvant of Toxoplasma lysate antigen (TLA). Experimental mice were intra-nasally inoculated with three doses of different regimens every two weeks, then challenged with 20 cysts of T. gondii Me49 strain, where they were sacrificed four weeks post-infection. Protective vaccine efficacy was evident via the significant brain cyst count reduction of 58.6%, together with remarkably high levels of humoral systemic and mucosal anti-Toxoplasma antibodies (Ig G, Ig A), supported by a reduced tachyzoites invasion of Vero cells in vitro upon incubation with sera obtained from these vaccinated mice. A cellular immune response was evident through the induction of significant levels of interferon-gamma (IFN γ), associated with morphological deteriorations of cysts harvested from the brains of vaccinated mice. Furthermore, the amelioration of infection-induced oxidative stress (OS) and histopathological changes were evident in mice immunized with TLA/MLT-SLNs. In conclusion, the present study highlighted the promising role of intranasal MLT-SLNs as a novel mucosal adjuvant candidate against chronic toxoplasmosis. MDPI 2022-11-27 /pmc/articles/PMC9785012/ /pubmed/36548656 http://dx.doi.org/10.3390/tropicalmed7120401 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Said, Doaa E.
Amer, Eglal I.
Sheta, Eman
Makled, Shaimaa
Diab, Hala E.
Arafa, Fadwa M.
Nano-Encapsulated Melatonin: A Promising Mucosal Adjuvant in Intranasal Immunization against Chronic Experimental T. gondii Infection
title Nano-Encapsulated Melatonin: A Promising Mucosal Adjuvant in Intranasal Immunization against Chronic Experimental T. gondii Infection
title_full Nano-Encapsulated Melatonin: A Promising Mucosal Adjuvant in Intranasal Immunization against Chronic Experimental T. gondii Infection
title_fullStr Nano-Encapsulated Melatonin: A Promising Mucosal Adjuvant in Intranasal Immunization against Chronic Experimental T. gondii Infection
title_full_unstemmed Nano-Encapsulated Melatonin: A Promising Mucosal Adjuvant in Intranasal Immunization against Chronic Experimental T. gondii Infection
title_short Nano-Encapsulated Melatonin: A Promising Mucosal Adjuvant in Intranasal Immunization against Chronic Experimental T. gondii Infection
title_sort nano-encapsulated melatonin: a promising mucosal adjuvant in intranasal immunization against chronic experimental t. gondii infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785012/
https://www.ncbi.nlm.nih.gov/pubmed/36548656
http://dx.doi.org/10.3390/tropicalmed7120401
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