Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines.
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 activa...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1797090825552789504 |
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| author | Larsen, K Spencer, A Goodman, A Gilchrist, A Furze, J Rollier, C Kiss-Toth, E Gilbert, S Bregu, M Soilleux, E Hill, A Wyllie, D |
| author_facet | Larsen, K Spencer, A Goodman, A Gilchrist, A Furze, J Rollier, C Kiss-Toth, E Gilbert, S Bregu, M Soilleux, E Hill, A Wyllie, D |
| author_sort | Larsen, K |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:24:18Z |
| format | Journal article |
| id | oxford-uuid:b88185cd-c0c3-4793-8416-fad145787afa |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:24:18Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:b88185cd-c0c3-4793-8416-fad145787afa2022-03-27T04:56:22ZExpression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b88185cd-c0c3-4793-8416-fad145787afaEnglishSymplectic Elements at Oxford2009Larsen, KSpencer, AGoodman, AGilchrist, AFurze, JRollier, CKiss-Toth, EGilbert, SBregu, MSoilleux, EHill, AWyllie, DImproving 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. |
| spellingShingle | Larsen, K Spencer, A Goodman, A Gilchrist, A Furze, J Rollier, C Kiss-Toth, E Gilbert, S Bregu, M Soilleux, E Hill, A Wyllie, D Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines. |
| title | Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines. |
| title_full | Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines. |
| title_fullStr | Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines. |
| title_full_unstemmed | Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines. |
| title_short | Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines. |
| title_sort | expression of tak1 and tram induces synergistic pro inflammatory signalling and adjuvants dna vaccines |
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