Abstract
Background: During last years, DNA vaccine immunogenicity has been optimized by the employment of co-stimulatory molecules and molecular adjuvants. It has been reported that plasmid (pATRex), encompassing the DNA sequence for the von Willebrand A (vWA/A) domain of the Anthrax Toxin Receptor-1 (ANTXR-1, alias TEM8, Tumor Endothelial Marker 8), acts as strong immune adjuvant by inducing formation of insoluble intracellular aggregates. Markedly, we faced with upsetting findings regarding the safety of pATRex as adjuvant since the aggregosome formation prompted to osteopenia in mice.
Objective: The present study provides additional evidences about the proteinaceous adjuvants action within bone marrow and questioned regarding the self-aggregation protein adjuvants immunotoxicity on marrow niches.
Methods & Results: Using histological, biochemical and proteomic assays we shed light on pATRex effects within bone marrow niche and specifically we evidenced an aplastic-like bone marrow with disrupted cytokine/chemokine production.
Conclusion: The above findings provide compelling support to the thesis that adjuvants based on plasmids encoding protein aggregation domains disrupt the physiological features of the bone marrow elements.
Keywords: Bone marrow, Bone marrow niche, Osteopenia, DNA vaccines, Adjuvants, Protein aggregates.
Current Gene Therapy
Title:Molecular Adjuvants Based on Plasmids Encoding Protein Aggregation Domains Affect Bone Marrow Niche Homeostasis
Volume: 17 Issue: 5
Author(s): Maria Giovanna Sabbieti, Giovanna Lacava, Andrea Amaroli, Luigi Marchetti, Roberta Censi, Piera Di Martino and Dimitrios Agas*
Affiliation:
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino (MC),Italy
Keywords: Bone marrow, Bone marrow niche, Osteopenia, DNA vaccines, Adjuvants, Protein aggregates.
Abstract: Background: During last years, DNA vaccine immunogenicity has been optimized by the employment of co-stimulatory molecules and molecular adjuvants. It has been reported that plasmid (pATRex), encompassing the DNA sequence for the von Willebrand A (vWA/A) domain of the Anthrax Toxin Receptor-1 (ANTXR-1, alias TEM8, Tumor Endothelial Marker 8), acts as strong immune adjuvant by inducing formation of insoluble intracellular aggregates. Markedly, we faced with upsetting findings regarding the safety of pATRex as adjuvant since the aggregosome formation prompted to osteopenia in mice.
Objective: The present study provides additional evidences about the proteinaceous adjuvants action within bone marrow and questioned regarding the self-aggregation protein adjuvants immunotoxicity on marrow niches.
Methods & Results: Using histological, biochemical and proteomic assays we shed light on pATRex effects within bone marrow niche and specifically we evidenced an aplastic-like bone marrow with disrupted cytokine/chemokine production.
Conclusion: The above findings provide compelling support to the thesis that adjuvants based on plasmids encoding protein aggregation domains disrupt the physiological features of the bone marrow elements.
Export Options
About this article
Cite this article as:
Sabbieti Giovanna Maria , Lacava Giovanna , Amaroli Andrea , Marchetti Luigi , Censi Roberta , Di Martino Piera and Agas Dimitrios *, Molecular Adjuvants Based on Plasmids Encoding Protein Aggregation Domains Affect Bone Marrow Niche Homeostasis, Current Gene Therapy 2017; 17 (5) . https://dx.doi.org/10.2174/1566523218666180105122626
DOI https://dx.doi.org/10.2174/1566523218666180105122626 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Approaches for Administering Chemotherapy in the Intensive Care Unit
Current Drug Safety B Cells and Beyond: Therapeutic Opportunities Targeting Inflammation
Inflammation & Allergy - Drug Targets (Discontinued) Src Family Kinases as Regulators of Angiogenesis: Therapeutic Implications
Current Cancer Therapy Reviews Pathogenic Bacterial Proteins and their Anti-Inflammatory Effects in the Eukaryotic Host
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Niacin: From Mechanisms of Action to Therapeutic Uses
Mini-Reviews in Medicinal Chemistry Genetic Predisposition to Parkinson’s Disease and Cancer
Current Cancer Drug Targets Prophylaxis and Therapy of Allergy by Mucosal Tolerance Induction with Recombinant Allergens or Allergen Constructs
Current Drug Targets - Inflammation & Allergy Saffron-Based Crocin Prevents Early Lesions of Liver Cancer: In vivo, In vitro and Network Analyses
Recent Patents on Anti-Cancer Drug Discovery Neurotrophic and Neuroprotective Effects of Muscle Contraction
Current Pharmaceutical Design Hypoxia and Oxidative Stress in the Causation of Diabetic Retinopathy
Current Diabetes Reviews Peroxisome Proliferator-Activated Receptor γ Agonists as Insulin Sensitizers: From the Discovery to Recent Progress
Current Topics in Medicinal Chemistry Antiviral Treatment of HCV Carriers with Persistently Normal ALT Levels
Mini-Reviews in Medicinal Chemistry Pharmacological Inhibition of Protein Tyrosine Phosphatase 1B: A Promising Strategy for the Treatment of Obesity and Type 2 Diabetes Mellitus
Current Medicinal Chemistry Insight into Cocaine-Induced Neural and Behavioral Adaptations Using Genome-Wide Expression Profiling and Epigenomic Analysis
Current Psychopharmacology Current and Future Therapeutic Targets of Rheumatoid Arthritis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Telocytes in Liver
Current Stem Cell Research & Therapy Type 2 Diabetes Mellitus and Alzheimer’s Disease: Bridging the Pathophysiology and Management
Current Pharmaceutical Design Feline Immunodeficiency Virus Model for Designing HIV/AIDS Vaccines
Current HIV Research Novel Insights into V-ATPase Functioning: Distinct Roles for its Accessory Subunits ATP6AP1/Ac45 and ATP6AP2/(pro) Renin Receptor
Current Protein & Peptide Science Novel Dibenzothiepins with Antibiofilm Activity Demonstrated by Microbiological Assays and Molecular Modeling
Current Organic Chemistry