Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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