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The preparation and characterization of PLG nanoparticles with an entrapped synthetic TLR7 agonist and their preclinical evaluation as adjuvant for an adsorbed DTaP vaccine.
- Source :
-
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2016 Aug; Vol. 105, pp. 1-8. Date of Electronic Publication: 2016 May 17. - Publication Year :
- 2016
-
Abstract
- The design of safe and potent adjuvants able to enhance and modulate antigen-specific immunity is of great interest for vaccine research and development. In the present study, negatively charged poly(lactide-co-glycolide) (PLG) nanoparticles have been combined with a synthetic immunepotentiator molecule targeting the Toll-like receptor 7. The selection of appropriate preparation and freeze-drying conditions resulted in a PLG-based adjuvant with well-defined and stable physico-chemical properties. The adjuvanticity of such nanosystem has later been evaluated in the mouse model with a diphtheria-tetanus-pertussis (DTaP) vaccine, on the basis of the current need to improve the efficacy of acellular pertussis (aP) vaccines. DTaP antigens were adsorbed onto PLG nanoparticles surface, allowing the co-delivery of TLR7a and multiple antigens through a single formulation. The entrapment of TLR7a into PLG nanoparticles resulted in enhanced IgG and IgG2a antibody titers. Notably, the immune potentiator effect of TLR7a was less evident when it was used in not-entrapped form, indicating that co-localization of TLR7a and antigens is required to adequately stimulate immune responses. In conclusion, the rational selection of adjuvants and formulation here described resulted as a highly valuable approach to potentiate and better tailor DTaP vaccine immunogenicity.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Diphtheria-Tetanus-acellular Pertussis Vaccines immunology
Drug Evaluation, Preclinical
Immunoglobulin G blood
Mice
Polylactic Acid-Polyglycolic Acid Copolymer
Adjuvants, Immunologic administration & dosage
Diphtheria-Tetanus-acellular Pertussis Vaccines administration & dosage
Lactic Acid chemistry
Membrane Glycoproteins agonists
Nanoparticles chemistry
Polyglycolic Acid chemistry
Toll-Like Receptor 7 agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3441
- Volume :
- 105
- Database :
- MEDLINE
- Journal :
- European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
- Publication Type :
- Academic Journal
- Accession number :
- 27224856
- Full Text :
- https://doi.org/10.1016/j.ejpb.2016.05.013