Gene gun bombardment with gold particles displays a particular Th2-promoting signal that over-rules the Th1-inducing effect of immunostimulatory CpG motifs in DNA vaccines

被引:78
作者
Weiss, R
Scheiblhofer, S
Freund, J
Ferreira, F
Livey, I
Thalhamer, J
机构
[1] Salzburg Univ, Inst Chem & Biochem, A-5020 Salzburg, Austria
[2] Salzburg Univ, Inst Genet & Gen Biol, A-5020 Salzburg, Austria
[3] Baxter Vaccines AG, Biomed Res Ctr, Vienna, Austria
基金
奥地利科学基金会;
关键词
DNA immunization; gene gun; immunomodulation;
D O I
10.1016/S0264-410X(02)00250-5
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The mode of administering a DNA vaccine can influence the type of immune response induced by the vaccine. For instance, application of a DNA vaccine by gene gun typically induces a Th2-type reaction, whereas needle inoculation triggers a Th1 response. It has been proposed that the approximately 100-fold difference in the amount of DNA administered by these two methods is the critical factor determining whether a Th1 or a Th2 response is made. To test this hypothesis, BALB/c mice were immunized with two plasmid DNA constructs encoding different proteins (OspC/ZS7 of Borrelia burgdorferi and Bet v 1a, the major birch pollen allergen). Both vaccines were applied by needle and/or by gene gun immunization at the same and at different sites of injection. An analysis of the IgG subclass distribution and measurement of IFN-gamma after antigen-specific lymphoproliferation does not support the widely accepted view that Th2-type immunity induced by gene gun application is solely due to the low amount of injected plasmid DNA thus failing below the critical concentration of CpG motifs necessary for Th2-induction. Furthermore, the data also indicate a strong and even systemic adjuvant effect of the gene gun shot itself. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:3148 / 3154
页数:7
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