Special Issue "Immunization by Electroporation"

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (31 January 2020).

Special Issue Editors

Dr. Emanuela Signori
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Guest Editor
1. National Research Council-Institute of Translational Pharmacology (CNR-IFT), Via Fosso del Cavaliere 100, Rome, Italy
2. University Campus Bio-Medico of Rome, School of Medicine, Via Álvaro del Portillo 21, 00128 Rome, Italy
Interests: oncoimmunology, gene electrotransfer, DNA immunization, electroporation, plasmid DNA, electrochemotherapy
Dr. Richard Heller
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Guest Editor
1. Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23529, USA
2. School of Medical Diagnostic & Translational Sciences, College of Health Sciences, Old Dominion University, Norfolk, VA 23529, USA
Interests: gene therapy; electrotransfer; cancer; melanoma; vaccines; immunotherapy; electroporation
Special Issues and Collections in MDPI journals
Prof. Dr. Čemažar Maja
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Guest Editor
1. Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia
2. Department of Natural and Medical Subjects, Faculty of Health Sciences, University of Primorska, Polje 42, SI-6310 Izola, Slovenia
Interests: cancer biology, immune gene therapy, electroporation, gene electrotransfer, electrochemotherapy, translational oncology
Dr. Marie-Pierre Rols
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Guest Editor
Institut de Pharmacologie et de Biologie Structurale, IPBS CNRS (UMR 5089), Université de Toulouse, Paul Sabatier, 205, Route de Narbonne, 31077, Toulouse, France
Interests: electroporation; electrochemotherapy; cellular biophysics; gene transfer; nanoparticles; cell membrane; imaging; vectorization
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Studies in the field of immunology are revealing an attractive set of novel, different therapeutic approaches to treat infectious and cancer diseases. Among these, electroporation has become a widely accepted platform technology used for drug and gene delivery. When applied to cells in vitro or tissues in vivo, electroporation leads to increased membrane permeability, thus allowing for the internalization of molecules, such as plasmid DNA, siRNAs, and some chemotherapeutic drugs, which otherwise cannot enter the cells. Past and recent results also underline the capability of electrotransfer to influence the immune system response: it has been proven that, following electroporation treatments, different innate and adaptive immune cells can be recruited, influencing the immune response at local and, quite often, at distant levels. Due to this property, lot of studies in the field of immunization by electroporation have been undertaken.

Intramuscular and skin gene electrotransfer (GET) represents a minimal invasive strategy to employ in immunotherapy and/or vaccination against infectious and cancer diseases, and to treat wound healing; electrochemotherapy (ECT), irreversible electroporation (IRE), and calcium electroporation (CaEP) are becoming widely used in clinical protocols to treat different kinds of cancer.

In this Special Issue, we want to discuss how electroporation can modulate immunological effects and enhance the immune system response by genetic vaccines and/or immunomodulatory molecules, administered alone or in combination with other therapeutic treatments. We want also to discuss the immunological effects of drugs delivered by electric fields in pre-clinical and clinical trials.

The peer-reviewed papers will provide a cross-section on the ongoing research in the field of electroporation applied to infectious and cancer diseases.

Dr. Emanuela Signori
Dr. Marie-Pierre Rols
Prof. Dr. Čemažar Maja
Dr. Richard Heller
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (6 papers)

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Research

Open AccessArticle
Immunization against ROS1 by DNA Electroporation Impairs K-Ras-Driven Lung Adenocarcinomas
Vaccines 2020, 8(2), 166; https://doi.org/10.3390/vaccines8020166 - 06 Apr 2020
Abstract
Non-small cell lung cancer (NSCLC) is still the leading cause of cancer death worldwide. Despite the introduction of tyrosine kinase inhibitors and immunotherapeutic approaches, there is still an urgent need for novel strategies to improve patient survival. ROS1, a tyrosine kinase receptor endowed [...] Read more.
Non-small cell lung cancer (NSCLC) is still the leading cause of cancer death worldwide. Despite the introduction of tyrosine kinase inhibitors and immunotherapeutic approaches, there is still an urgent need for novel strategies to improve patient survival. ROS1, a tyrosine kinase receptor endowed with oncoantigen features, is activated by chromosomal rearrangement or overexpression in NSCLC and in several tumor histotypes. In this work, we have exploited transgenic mice harboring the activated K-Ras oncogene (K-RasG12D) that spontaneously develop metastatic NSCLC as a preclinical model to test the efficacy of ROS1 immune targeting. Indeed, qPCR and immunohistochemical analyses revealed ROS1 overexpression in the autochthonous primary tumors and extrathoracic metastases developed by K-RasG12D mice and in a derived transplantable cell line. As proof of concept, we have evaluated the effects of the intramuscular electroporation (electrovaccination) of plasmids coding for mouse- and human-ROS1 on the progression of these NSCLC models. A significant increase in survival was observed in ROS1-electrovaccinated mice challenged with the transplantable cell line. It is worth noting that tumors were completely rejected, and immune memory was achieved, albeit only in a few mice. Most importantly, ROS1 electrovaccination was also found to be effective in slowing the development of autochthonous NSCLC in K-RasG12D mice. Full article
(This article belongs to the Special Issue Immunization by Electroporation)
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Open AccessArticle
Intratumoral Gene Electrotransfer of Plasmid DNA Encoding shRNA against Melanoma Cell Adhesion Molecule Radiosensitizes Tumors by Antivascular Effects and Activation of an Immune Response
Vaccines 2020, 8(1), 135; https://doi.org/10.3390/vaccines8010135 - 19 Mar 2020
Abstract
In this study, radiotherapy was combined with the gene electrotransfer (GET) of plasmid encoding shRNA against melanoma cell adhesion molecule (pMCAM) with dual action, which was a vascular-targeted effect mediated by the silencing of MCAM and an immunological effect mediated by the presence [...] Read more.
In this study, radiotherapy was combined with the gene electrotransfer (GET) of plasmid encoding shRNA against melanoma cell adhesion molecule (pMCAM) with dual action, which was a vascular-targeted effect mediated by the silencing of MCAM and an immunological effect mediated by the presence of plasmid DNA in the cytosol-activating DNA sensors. The effects and underlying mechanisms of therapy were evaluated in more immunogenic B16F10 melanoma and less immunogenic TS/A carcinoma. The silencing of MCAM potentiated the effect of irradiation (IR) in both tumor models. Combined therapy resulted in 81% complete responses (CR) in melanoma and 27% CR in carcinoma. Moreover, after the secondary challenge of cured mice, 59% of mice were resistant to challenge with melanoma cells, and none were resistant to carcinoma. Combined therapy reduced the number of blood vessels; induced hypoxia, apoptosis, and necrosis; and reduced cell proliferation in both tumor models. In addition, the significant increase of infiltrating immune cells was observed in both tumor models but more so in melanoma, where the expression of IL-12 and TNF-α was determined as well. Our results indicate that the combined therapy exerts both antiangiogenic and immune responses that contribute to the antitumor effect. However, tumor immunological status is crucial for a sufficient immune system contribution to the overall antitumor effect. Full article
(This article belongs to the Special Issue Immunization by Electroporation)
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Open AccessArticle
Development of Tumor Cell-Based Vaccine with IL-12 Gene Electrotransfer as Adjuvant
Vaccines 2020, 8(1), 111; https://doi.org/10.3390/vaccines8010111 - 02 Mar 2020
Abstract
Tumor cell-based vaccines use tumor cells as a source of tumor-associated antigens. In our study, we aimed to develop and test a tumor vaccine composed of tumor cells killed by irradiation combined with in vivo interleukin-12 gene electrotransfer as an adjuvant. Vaccination was [...] Read more.
Tumor cell-based vaccines use tumor cells as a source of tumor-associated antigens. In our study, we aimed to develop and test a tumor vaccine composed of tumor cells killed by irradiation combined with in vivo interleukin-12 gene electrotransfer as an adjuvant. Vaccination was performed in the skin of B16-F10 malignant melanoma or CT26 colorectal carcinoma tumor-bearing mice, distant from the tumor site and combined with concurrent tumor irradiation. Vaccination was also performed before tumor inoculation in both tumor models and tumor outgrowth was followed. The antitumor efficacy of vaccination in combination with tumor irradiation or preventative vaccination varied between the tumor models. A synergistic effect between vaccination and irradiation was observed in the B16-F10, but not in the CT26 tumor model. In contrast, up to 56% of mice were protected from tumor outgrowth in the CT26 tumor model and none were protected in the B16-F10 tumor model. The results suggest a greater contribution of the therapeutic vaccination to tumor irradiation in a less immunogenic B16-F10 tumor model, in contrast to preventative vaccination, which has shown greater efficacy in a more immunogenic CT26 tumor model. Upon further optimization of the vaccination and irradiation regimen, our vaccine could present an alternative tumor cell-based vaccine. Full article
(This article belongs to the Special Issue Immunization by Electroporation)
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Open AccessArticle
Electrotransfer of siRNA to Silence Enhanced Green Fluorescent Protein in Tumor Mediated by a High Intensity Pulsed Electromagnetic Field
Vaccines 2020, 8(1), 49; https://doi.org/10.3390/vaccines8010049 - 27 Jan 2020
Cited by 3
Abstract
The contactless high intensity pulsed electromagnetic field (HI-PEMF)-induced increase of cell membrane permeability is similar to conventional electroporation, with the important difference of inducing an electric field non-invasively by exposing a treated tissue to a time-varying magnetic field. Due to the limited number [...] Read more.
The contactless high intensity pulsed electromagnetic field (HI-PEMF)-induced increase of cell membrane permeability is similar to conventional electroporation, with the important difference of inducing an electric field non-invasively by exposing a treated tissue to a time-varying magnetic field. Due to the limited number of studies in the field of electroporation induced by HI-PEMF, we designed experiments to explore the feasibility of such a contactless delivery technique for the gene electrotransfer of nucleic acids in tissues in vivo. By using HI-PEMF for gene electrotransfer, we silenced enhanced green fluorescent protein (EGFP) with siRNA molecules against EGFP in B16F10-EGFP tumors. Six days after the transfer, the fluorescent tumor area decreased by up to 39% as determined by fluorescence imaging in vivo. In addition, the silencing of EGFP to the same extent was confirmed at the mRNA and protein level. The results obtained in the in vivo mouse model demonstrate the potential use of HI-PEMF-induced cell permeabilization for gene therapy and DNA vaccination. Further studies are thus warranted to improve the equipment, optimize the protocols for gene transfer and the HI-PEMF parameters, and demonstrate the effects of HI-PEMF on a broader range of different normal and tumor tissues. Full article
(This article belongs to the Special Issue Immunization by Electroporation)
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Open AccessArticle
Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA
Vaccines 2020, 8(1), 27; https://doi.org/10.3390/vaccines8010027 - 14 Jan 2020
Abstract
The importance of a balanced TH1/TH2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the [...] Read more.
The importance of a balanced TH1/TH2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the induction of adoptive immunity and their inhibitors (monoclonal antibodies) are licensed for cancer therapy, we investigated the effect of checkpoint blockade after HIV-1 genetic vaccination on enhancement and modulation of antiviral antibody responses. By intraperitoneal administration of checkpoint antibodies in mice we observed an induction of anti-drug antibodies which may interfere with immunomodulation by checkpoint inhibitors. Therefore, we blocked immune checkpoints locally by co-electroporation of DNA vaccines encoding the active soluble ectodomains of programmed cell death protein-1 (PD-1) or its ligand (PD-L1), respectively. Plasmid-encoded immune checkpoints did not elicit a detectable antibody response, suggesting no interference with their immunomodulatory effects. Co-electroporation of a HIV-1 DNA vaccine formulation with soluble PD-L1 ectodomain increased HIV-1 Env-specific TH1 CD4 T cell and IgG2a antibody responses. The overall antibody response was hereby shifted towards a more TH1/TH2 balanced subtype pattern. These findings indicate that co-electroporation of soluble checkpoint ectodomains together with DNA-based vaccines has modulatory effects on vaccine-induced immune responses that could improve vaccine efficacies. Full article
(This article belongs to the Special Issue Immunization by Electroporation)
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Open AccessArticle
Immunogenicity and Protection Efficacy of a Naked Self-Replicating mRNA-Based Zika Virus Vaccine
Vaccines 2019, 7(3), 96; https://doi.org/10.3390/vaccines7030096 - 23 Aug 2019
Abstract
To combat emerging infectious diseases like Zika virus (ZIKV), synthetic messenger RNAs (mRNAs) encoding viral antigens are very attractive as they allow a rapid, generic, and flexible production of vaccines. In this work, we engineered a self-replicating mRNA (sr-mRNA) vaccine encoding the pre-membrane [...] Read more.
To combat emerging infectious diseases like Zika virus (ZIKV), synthetic messenger RNAs (mRNAs) encoding viral antigens are very attractive as they allow a rapid, generic, and flexible production of vaccines. In this work, we engineered a self-replicating mRNA (sr-mRNA) vaccine encoding the pre-membrane and envelope (prM-E) glycoproteins of ZIKV. Intradermal electroporation of as few as 1 µg of this mRNA-based ZIKV vaccine induced potent humoral and cellular immune responses in BALB/c and especially IFNAR1-/- C57BL/6 mice, resulting in a complete protection of the latter mice against ZIKV infection. In wild-type C57BL/6 mice, the vaccine resulted in very low seroconversion rates and antibody titers. The potency of the vaccine was inversely related to the dose of mRNA used in wild-type BALB/c or C57BL/6 mice, as robust type I interferon (IFN) response was determined in a reporter mice model (IFN-β+/Δβ-luc). We further investigated the inability of the sr-prM-E-mRNA ZIKV vaccine to raise antibodies in wild-type C57BL/6 mice and found indications that type I IFNs elicited by this naked sr-mRNA vaccine might directly impede the induction of a robust humoral response. Therefore, we assume that the efficacy of sr-mRNA vaccines after intradermal electroporation might be increased by strategies that temper their inherent innate immunogenicity. Full article
(This article belongs to the Special Issue Immunization by Electroporation)
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