Development of Delivery Systems Enhances the Potency of Cell-Based HIV-1 Therapeutic Vaccine Candidates

An effective therapeutic vaccine to eradicate HIV-1 infection does not exist yet. Among different vaccination strategies, cell-based vaccines could achieve in clinical trials. Cell viability and low nucleic acid expression are the problems related to dendritic cells (DCs) and mesenchymal stem cells...

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Main Authors: Amin Hadi, Abbas Rastgoo, Maryam Eskandarian, Nooshin Haghighipour, Azam Bolhassani
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2021/5538348
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author Amin Hadi
Abbas Rastgoo
Maryam Eskandarian
Nooshin Haghighipour
Azam Bolhassani
author_facet Amin Hadi
Abbas Rastgoo
Maryam Eskandarian
Nooshin Haghighipour
Azam Bolhassani
author_sort Amin Hadi
collection DOAJ
description An effective therapeutic vaccine to eradicate HIV-1 infection does not exist yet. Among different vaccination strategies, cell-based vaccines could achieve in clinical trials. Cell viability and low nucleic acid expression are the problems related to dendritic cells (DCs) and mesenchymal stem cells (MSCs), which are transfected with plasmid DNA. Thus, novel in vitro strategies are needed to improve DNA transfection into these cells. The recent study assessed immune responses generated by MSCs and DCs, which were derived from mouse bone marrow and modified with Nef antigen using novel methods in mice. For this purpose, an excellent gene transfection approach by mechanical methods was used. Our data revealed that the transfection efficacy of Nef DNA into the immature MSCs and DCs was improved by the combination of chemical and mechanical (causing equiaxial cyclic stretch) approaches. Also, chemical transfection performed two times with 48-hour intervals further increased gene expression in both cells. The groups immunized with Nef DC prime/rNef protein boost and then Nef MSC prime/rNef protein boost were able to stimulate high levels of IFN-γ, IgG2b, IgG2a, and Granzyme B directed toward Th1 responses in mice. Furthermore, the mesenchymal or dendritic cell-based immunizations were more effective compared to protein immunization for enhancement of the Nef-specific T-cell responses in mice. Hence, the use of chemical reagent and mechanical loading simultaneously can be an excellent method in delivering cargoes into DCs and MSCs. Moreover, DC- and MSC-based immunizations can be considered as promising approaches for protection against HIV-1 infections.
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institution Kabale University
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spelling doaj-art-1692199617e64db795cfff29fdc1d79c2025-02-03T06:43:29ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/55383485538348Development of Delivery Systems Enhances the Potency of Cell-Based HIV-1 Therapeutic Vaccine CandidatesAmin Hadi0Abbas Rastgoo1Maryam Eskandarian2Nooshin Haghighipour3Azam Bolhassani4Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, IranSchool of Mechanical Engineering, University of Tehran, Tehran, IranDepartment of Immunology, Tarbiat Modares University, Tehran, IranNational Cell Bank of Iran, Pasteur Institute of Iran, Tehran, IranDepartment of Hepatitis and AIDs, Pasteur Institute of Iran, Tehran, IranAn effective therapeutic vaccine to eradicate HIV-1 infection does not exist yet. Among different vaccination strategies, cell-based vaccines could achieve in clinical trials. Cell viability and low nucleic acid expression are the problems related to dendritic cells (DCs) and mesenchymal stem cells (MSCs), which are transfected with plasmid DNA. Thus, novel in vitro strategies are needed to improve DNA transfection into these cells. The recent study assessed immune responses generated by MSCs and DCs, which were derived from mouse bone marrow and modified with Nef antigen using novel methods in mice. For this purpose, an excellent gene transfection approach by mechanical methods was used. Our data revealed that the transfection efficacy of Nef DNA into the immature MSCs and DCs was improved by the combination of chemical and mechanical (causing equiaxial cyclic stretch) approaches. Also, chemical transfection performed two times with 48-hour intervals further increased gene expression in both cells. The groups immunized with Nef DC prime/rNef protein boost and then Nef MSC prime/rNef protein boost were able to stimulate high levels of IFN-γ, IgG2b, IgG2a, and Granzyme B directed toward Th1 responses in mice. Furthermore, the mesenchymal or dendritic cell-based immunizations were more effective compared to protein immunization for enhancement of the Nef-specific T-cell responses in mice. Hence, the use of chemical reagent and mechanical loading simultaneously can be an excellent method in delivering cargoes into DCs and MSCs. Moreover, DC- and MSC-based immunizations can be considered as promising approaches for protection against HIV-1 infections.http://dx.doi.org/10.1155/2021/5538348
spellingShingle Amin Hadi
Abbas Rastgoo
Maryam Eskandarian
Nooshin Haghighipour
Azam Bolhassani
Development of Delivery Systems Enhances the Potency of Cell-Based HIV-1 Therapeutic Vaccine Candidates
Journal of Immunology Research
title Development of Delivery Systems Enhances the Potency of Cell-Based HIV-1 Therapeutic Vaccine Candidates
title_full Development of Delivery Systems Enhances the Potency of Cell-Based HIV-1 Therapeutic Vaccine Candidates
title_fullStr Development of Delivery Systems Enhances the Potency of Cell-Based HIV-1 Therapeutic Vaccine Candidates
title_full_unstemmed Development of Delivery Systems Enhances the Potency of Cell-Based HIV-1 Therapeutic Vaccine Candidates
title_short Development of Delivery Systems Enhances the Potency of Cell-Based HIV-1 Therapeutic Vaccine Candidates
title_sort development of delivery systems enhances the potency of cell based hiv 1 therapeutic vaccine candidates
url http://dx.doi.org/10.1155/2021/5538348
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