Vaxfectin enhances the humoral immune response to plasmid DNA-encoded antigens

被引:79
|
作者
Hartikka, J
Bozoukova, V
Ferrari, M
Sukhu, L
Enas, J
Sawdey, M
Wloch, MK
Tonsky, K
Norman, J
Manthorpe, M
Wheeler, CJ
机构
[1] Vical Inc, Dept Chem, San Diego, CA 92121 USA
[2] Vical Inc, Dept Cell Biol, San Diego, CA 92121 USA
[3] Vical Inc, Dept Pharmacol, San Diego, CA 92121 USA
关键词
genetic immunization; plasmid DNA; cationic lipid;
D O I
10.1016/S0264-410X(00)00445-X
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
This report characterizes Vaxfectin, a novel cationic and neutral lipid formulation which enhances antibody responses when complexed with an antigen-encoding plasmid DNA (pDNA). In mice, intramuscular injection of Vaxfectin formulated with pDNA encoding influenza nucleoprotein (NP) increased antibody titers up to 20-fold. to levels that could not be reached with pDNA alone. As little as 1 mug of pDNA formulated with Vaxfectin per muscle resulted in higher anti-NP titers than that obtained with 25 mug naked pDNA. The antibody titers in animals injected with Vaxfectin-pDNA remained higher than in the naked pDNA controls for at least 9 months. The enhancement in antibody titers was dependent on the Vaxfectin dose and was accomplished without diminishing the strong anti-NP cytolytic T cell response typical of pDNA-based vaccines. In rabbits, complexing pDNA with Vaxfectin enhanced antibody titers up to 50 fold with needle and syringe injections and also augmented humoral responses when combined with a needle-free injection device. Vaxfectin did not facilitate transfection and/or increase synthesis of beta -galactosidase reporter protein in muscle tissue. ELISPOT assays performed on bone marrow cells from vaccinated mice showed that Vaxfectin produced a three- to five-fold increase in the number of NP-specific plasma cells. Thus. Vaxfectin should be a useful adjuvant for enhancing pDNA-based vaccinations. (C) 7001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1911 / 1923
页数:13
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