DNA/amphiphilic block copolymer nanospheres promote low-dose DNA vaccination.
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.
CNRS UMR 6204, Faculté des Sciences et des Techniques, Université de Nantes, Nantes, France.
Dorian
D
McIlroy
Benoît
B
Barteau
Jeannette
J
Cany
Peggy
P
Richard
Clothilde
C
Gourden
Sophie
S
Conchon
Bruno
B
Pitard
D000818:Animals; D004247:DNA / Q000737:chemistry* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054118:Nanospheres / Q000737:chemistry*; D010957:Plasmids / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry*; D019444:Vaccines, DNA / Q000737:chemistry* / Q000276:immunology*; D001616:beta-Galactosidase / Q000235:genetics
D011409:Propylene Glycols; D019444:Vaccines, DNA; D011092:Polyethylene Glycols; D004247:DNA; D001616:beta-Galactosidase