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Optimization, Production, and Characterization of a CpG-Oligonucleotide-Ficoll Conjugate Nanoparticle Adjuvant for Enhanced Immunogenicity of Anthrax Protective Antigen.
Milley, Bob; Kiwan, Radwan; Ott, Gary S; Calacsan, Carlo; Kachura, Melissa; Campbell, John D; Kanzler, Holger; Coffman, Robert L.
Afiliação
  • Milley B; Dynavax Technologies Corporation , 2929 Seventh Street, Suite 100, Berkeley, California 94710, United States.
  • Kiwan R; Dynavax Technologies Corporation , 2929 Seventh Street, Suite 100, Berkeley, California 94710, United States.
  • Ott GS; Dynavax Technologies Corporation , 2929 Seventh Street, Suite 100, Berkeley, California 94710, United States.
  • Calacsan C; Dynavax Technologies Corporation , 2929 Seventh Street, Suite 100, Berkeley, California 94710, United States.
  • Kachura M; Dynavax Technologies Corporation , 2929 Seventh Street, Suite 100, Berkeley, California 94710, United States.
  • Campbell JD; Dynavax Technologies Corporation , 2929 Seventh Street, Suite 100, Berkeley, California 94710, United States.
  • Kanzler H; MedImmune LLC , One MedImmune Way, Gaithersburg, Maryland 20878, United States.
  • Coffman RL; Dynavax Technologies Corporation , 2929 Seventh Street, Suite 100, Berkeley, California 94710, United States.
Bioconjug Chem ; 27(5): 1293-304, 2016 05 18.
Article em En | MEDLINE | ID: mdl-27074387
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oligodesoxirribonucleotídeos / Toxinas Bacterianas / Desenho de Fármacos / Adjuvantes Imunológicos / Nanopartículas / Ficoll / Antígenos de Bactérias Limite: Animals / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oligodesoxirribonucleotídeos / Toxinas Bacterianas / Desenho de Fármacos / Adjuvantes Imunológicos / Nanopartículas / Ficoll / Antígenos de Bactérias Limite: Animals / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article