Immunization with a new DNA vaccine for Alzheimer's disease elicited Th2 immune response in BALB/c mice by in vivo electroporation

Xing, Xiaofei; Sha, Sha; Yu, Li; Zong, Lixia; Jiang, Tongzi; Cao, Yunpeng

doi:10.1016/j.jns.2011.09.040

Cited by 12 publications

(6 citation statements)

References 31 publications

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“…We do not believe that this response is due to an inherent quality associated with the RBD antigen. Instead, it is most likely a result of the potent adjuvant properties of either EP, which can promote a broader range of isotypes to various antigens (46)(47)(48)(49), or plasmid-incorporated cytosine phosphate guanosine nucleotide sequences, which signal through Toll-like receptor 9 and scavenger receptors.…”

Section: Discussionmentioning

confidence: 99%

An Optimized, Synthetic DNA Vaccine Encoding the Toxin A and Toxin B Receptor Binding Domains of Clostridium difficile Induces Protective Antibody ResponsesIn Vivo

et al. 2014

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h Clostridium difficile-associated disease (CDAD) constitutes a large majority of nosocomial diarrhea cases in industrialized nations and is mediated by the effects of two secreted toxins, toxin A (TcdA) and toxin B (TcdB). Patients who develop strong antitoxin antibody responses can clear C. difficile infection and remain disease free. Key toxin-neutralizing epitopes have been found within the carboxy-terminal receptor binding domains (RBDs) of TcdA and TcdB, which has generated interest in developing the RBD as a viable vaccine target. While numerous platforms have been studied, very little data describes the potential of DNA vaccination against CDAD. Therefore, we created highly optimized plasmids encoding the RBDs from TcdA and TcdB in which any putative N-linked glycosylation sites were altered. Mice and nonhuman primates were immunized intramuscularly, followed by in vivo electroporation, and in these animal models, vaccination induced significant levels of both anti-RBD antibodies (blood and stool) and RBD-specific antibody-secreting cells. Further characterization revealed that sera from immunized mice and nonhuman primates could detect RBD protein from transfected cells, as well as neutralize purified toxins in an in vitro cytotoxicity assay. Mice that were immunized with plasmids or given nonhuman-primate sera were protected from a lethal challenge with purified TcdA and/or TcdB. Moreover, immunized mice were significantly protected when challenged with C. difficile spores from homologous (VPI 10463) and heterologous, epidemic (UK1) strains. These data demonstrate the robust immunogenicity and efficacy of a TcdA/B RBD-based DNA vaccine in preclinical models of acute toxin-associated and intragastric, sporeinduced colonic disease.

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Section: Discussionmentioning

confidence: 99%

An Optimized, Synthetic DNA Vaccine Encoding the Toxin A and Toxin B Receptor Binding Domains of Clostridium difficile Induces Protective Antibody ResponsesIn Vivo

et al. 2014

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“…Effective use of EP for enhancement of plasmid DNA vaccination was first reported 10 years ago (Kadowaki et al 2000; Widera et al 2000; Drabick et al 2001) and has already reached the clinical trial stage (van Drunen Littel-van den Hurk and Hannaman 2010; Ferraro et al 2011; Vasan et al 2011; El-Kamary et al 2012). The success of EP for plasmid DNA vaccination was attributed to the fact that EP enhances delivery of plasmid DNA into the cells, where it is expressed for a long time (several months) (Widera et al 2000; Cemazar et al 2006; Escoffre et al 2010), and thus induces a potent immune response of the host to the introduced encoded antigen (Drabick et al 2001; Liu et al 2008; Roos et al 2009; Xing et al 2012). Furthermore, EP was demonstrated to be safe and well tolerated in preclinical as well as clinical studies (Vanbever and Preat 1999; Sardesai and Weiner 2011; El-Kamary et al 2012).…”

Section: Introductionmentioning

confidence: 99%

In Vivo Molecular Imaging and Histological Analysis of Changes Induced by Electric Pulses Used for Plasmid DNA Electrotransfer to the Skin: A Study in a Dorsal Window Chamber in Mice

et al. 2012

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Electropermeabilization/electroporation (EP) is a physical method that by application of electric pulses to cells increases cell membrane permeability and enables the introduction of molecules into the cells. One of the uses of EP in vivo is plasmid DNA electrotransfer to the skin for DNA vaccination. EP of tissues induces reduction of blood flow and, in combination with plasmid DNA, induction of an immune response. One of the EP protocols for plasmid DNA electrotransfer to the skin is a combination of high-voltage (HV) and low-voltage (LV) pulses. However, the effects of this pulse combination on skin-vessel blood flow are not known. Therefore, using intravital microscopy in a dorsal window chamber in mice and fluorescently labeled dextrans, the effects of one HV and eight LV pulses on skin vasculature were investigated. In addition, a detailed histological analysis was performed. Image analysis of fluorescence intensity changes demonstrated that EP induces a transient constriction and increased permeability of blood vessels as well as a “vascular lock.” Histological analysis revealed rounding up of endothelial cells and stacking up of erythrocytes at 1 h after EP. In addition, extravasation of erythrocytes and leukocyte infiltration accompanied by edema were determined up to 24 h after EP. In conclusion, our results show that blood flow modifying effects of EP in skin contribute to the infiltration of immune cells in the exposed area. When combined with plasmid DNA for vaccination, this could enable the initial and prolonged contact of immune cells with encoded therapeutic proteins.

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“…Other methods have shown promising efficient and safe vaccine towards inflammatory response in human and transgenic AD models [156–160]. Still more studies are needed to ascertain vaccine validation and standardization at preventing autoimmune response, vasogenic edema and microhemorrhage although detrimental side effects have been reported in transgenic mice [161–163] as well for bapineuzumab in patients [164–167].…”

Section: Methods Development For Early Diagnosis and Therapies In mentioning

confidence: 99%

Perspectives in Molecular Imaging Using Staging Biomarkers and Immunotherapies in Alzheimer’s Disease

Leclerc

Abulrob

2013

The Scientific World Journal

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Sporadic Alzheimer's disease (AD) is an emerging chronic illness characterized by a progressive pleiotropic pathophysiological mode of actions triggered during the senescence process and affecting the elderly worldwide. The complex molecular mechanisms of AD not only are supported by cholinergic, beta-amyloid, and tau theories but also have a genetic basis that accounts for the difference in symptomatology processes activation among human population which will evolve into divergent neuropathological features underlying cognitive and behaviour alterations. Distinct immune system tolerance could also influence divergent responses among AD patients treated by immunotherapy. The complexity in nature increases when taken together the genetic/immune tolerance with the patient's brain reserve and with neuropathological evolution from early till advance AD clinical stages. The most promising diagnostic strategies in today's world would consist in performing high diagnostic accuracy of combined modality imaging technologies using beta-amyloid 42 peptide-cerebrospinal fluid (CSF) positron emission tomography (PET), Pittsburgh compound B-PET, fluorodeoxyglucose-PET, total and phosphorylated tau-CSF, and volumetric magnetic resonance imaging hippocampus biomarkers for criteria evaluation and validation. Early diagnosis is the challenge task that needs to look first at plausible mechanisms of actions behind therapies, and combining them would allow for the development of efficient AD treatment in a near future.

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Immunization with a new DNA vaccine for Alzheimer's disease elicited Th2 immune response in BALB/c mice by in vivo electroporation

Cited by 12 publications

References 31 publications

An Optimized, Synthetic DNA Vaccine Encoding the Toxin A and Toxin B Receptor Binding Domains of Clostridium difficile Induces Protective Antibody ResponsesIn Vivo

An Optimized, Synthetic DNA Vaccine Encoding the Toxin A and Toxin B Receptor Binding Domains of Clostridium difficile Induces Protective Antibody ResponsesIn Vivo

In Vivo Molecular Imaging and Histological Analysis of Changes Induced by Electric Pulses Used for Plasmid DNA Electrotransfer to the Skin: A Study in a Dorsal Window Chamber in Mice

Perspectives in Molecular Imaging Using Staging Biomarkers and Immunotherapies in Alzheimer’s Disease

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