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), School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino (MC), Department of Surgical and Diagnostic Sciences, University of Genova, Genova, School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino (MC), School of Pharmacy, University of Camerino, Camerino, (MC), School of Pharmacy, University of Camerino, Camerino, (MC), School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino (MC)
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.
