کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2404893 | 1103004 | 2009 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: 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](/preview/png/2404893.png)
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.
Journal: Vaccine - Volume 27, Issue 41, 18 September 2009, Pages 5589–5598