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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.

Original publication

DOI

10.1016/j.vaccine.2009.07.025

Type

Journal article

Journal

Vaccine

Publication Date

18/09/2009

Volume

27

Pages

5589 - 5598

Keywords

Adjuvants, Immunologic, Animals, CD8-Positive T-Lymphocytes, Cell Line, Female, Gene Expression Profiling, Humans, Interferon-gamma, MAP Kinase Kinase Kinases, Macrophages, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Receptors, Interleukin, Vaccines, DNA