Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines
Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines
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DOI：
10.1016/j.vaccine.2009.07.025
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发表时间：
2009-09-18
期刊：
影响因子：
5.5
通讯作者：
Wyllie, David H.
中科院分区：
文献类型：
--
作者：
Larsen, Karen Colbjorn;Spencer, Alexandra J.;Wyllie, David H.
Improving vaccine immunogenicity remains a major challenge in the fight against developing country diseases like malaria and AIDS. We describe a novel strategy to identify new DNA vaccine adjuvants. We have screened components of the Toll-like receptor signalling pathways for their ability to activate pro-inflammatory target genes in transient transfection assays and assessed in vivo adjuvant activity by expressing the activators from the DNA backbone of vaccines. We find that a robust increase in the immune response necessitates co-expression of two activators. Accordingly, the combination of tak1 and tram elicits synergistic reporter activation in transient transfection assays. In a mouse model this combination, but not the individual molecules, induced approximately twofold increases in CD8(+) T-cell immune responses. These results indicate that optimal immunogenicity may require activation of distinct innate immune signalling pathways. Thus this strategy offers a novel route to the discovery of a new generation of adjuvants. (c) 2009 Elsevier Ltd. All rights reserved.
