DNA/amphiphilic block copolymer nanospheres promote low-dose DNA vaccination
| Autor: | Sophie Conchon, Dorian McIlroy, Benoit Barteau, Bruno Pitard, Peggy Richard, Clothilde Gourden, Jeannette Cany |
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| Přispěvatelé: | Unité de Biotechnologie, Biocatalyse et Biorégulation (U3B), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Immunogen
medicine.medical_treatment Enzyme-Linked Immunosorbent Assay Mice Transgenic Biology Polyethylene Glycols DNA vaccination Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Plasmid Antigen Drug Discovery Vaccines DNA medicine Genetics Animals Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology Pharmacology 0303 health sciences ELISPOT DNA Original Articles beta-Galactosidase Molecular biology 3. Good health Mice Inbred C57BL chemistry Propylene Glycols Naked DNA 030220 oncology & carcinogenesis Molecular Medicine [SDV.IB]Life Sciences [q-bio]/Bioengineering Adjuvant Nanospheres Plasmids |
| Zdroj: | Molecular Therapy Molecular Therapy, Cell Press, 2009, 17 (8), pp.1473-81 |
| ISSN: | 1525-0016 1525-0024 |
| Popis: | Intramuscular (i.m.) DNA vaccination induces strong cellular immune responses in the mouse, but only at DNA doses that cannot be achieved in humans. Because antigen expression is weak after naked DNA injection, we screened five nonionic block copolymers of poly(ethyleneoxide)-poly(propyleneoxide) (PEO-PPO) for their ability to enhance DNA vaccination using a beta-galactosidase (betaGal) encoding plasmid, pCMV-betaGal, as immunogen. At a high DNA dose, formulation with the tetrafunctional block copolymers 304 (molecular weight [MW] 1,650) and 704 (MW 5,500) and the triblock copolymer Lutrol (MW 8,600) increased betaGal-specific interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) responses 2-2.5-fold. More importantly, 704 allowed significant reductions in the dose of antigen-encoding plasmid. A single injection of 2 microg pCMV-betaGal with 704 gave humoral and ELISPOT responses equivalent to those obtained with 100 microg naked DNA and conferred protection in tumor vaccination models. However, 704 had no adjuvant properties for betaGal protein, and immune responses were only elicited by low doses of pCMV-betaGal formulated with 704 if noncoding carrier DNA was added to maintain total DNA dose at 20 microg. Overall, these results show that formulation with 704 and carrier DNA can reduce the dose of antigen-encoding plasmid by at least 50-fold. |
| Databáze: | OpenAIRE |
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