AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER
May 132016
 

Abstract Image

We have synthesized and characterized a novel phosphorothioate CpG oligodeoxynucleotide (CpG ODN)-Ficoll conjugated nanoparticulate adjuvant, termed DV230-Ficoll. This adjuvant was constructed from an amine-functionalized-Ficoll, a heterobifunctional linker (succinimidyl-[(N-maleimidopropionamido)-hexaethylene glycol] ester) and the CpG-ODN DV230. Herein, we describe the evaluation of the purity and reactivity of linkers of different lengths for CpG-ODN-Ficoll conjugation, optimization of linker coupling, and conjugation of thiol-functionalized CpG to maleimide-functionalized Ficoll and process scale-up. Physicochemical characterization of independently produced lots of DV230-Ficoll reveal a bioconjugate with a particle size of approximately 50 nm and covalent attachment of more than 100 molecules of CpG per Ficoll. Solutions of purified DV230-Ficoll were stable for at least 12 months at frozen and refrigerated temperatures and stability was further enhanced in lyophilized form. Compared to nonconjugated monomeric DV230, the DV230-Ficoll conjugate demonstrated improved in vitro potency for induction of IFN-α from human peripheral blood mononuclear cells and induced higher titer neutralizing antibody responses against coadministered anthrax recombinant protective antigen in mice. The processes described here establish a reproducible and robust process for the synthesis of a novel, size-controlled, and stable CpG-ODN nanoparticle adjuvant suitable for manufacture and use in vaccines.

READ……http://pubs.acs.org/doi/full/10.1021/acs.bioconjchem.6b00107

Optimization, Production, and Characterization of a CpG-Oligonucleotide-Ficoll Conjugate Nanoparticle Adjuvant for Enhanced Immunogenicity of Anthrax Protective Antigen

Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, California 94710, United States
MedImmune LLC, One MedImmune Way, Gaithersburg, Maryland 20878, United States
Bioconjugate Chem., Article ASAP
DOI: 10.1021/acs.bioconjchem.6b00107
Publication Date (Web): April 13, 2016
Copyright © 2016 American Chemical Society
*E-mail: bmilley@dynavax.com. Phone: (510) 665-7227. Fax: (510) 848-1327.

ACS Editors’ Choice – This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

//////Optimization, Production, Characterization,  CpG-Oligonucleotide-Ficoll Conjugate Nanoparticle Adjuvant,  Enhanced Immunogenicity, Anthrax Protective Antigen

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