Protective immunity to tuberculosis with Ag85B-ESAT-6 in a synthetic cationic adjuvant system IC31.
In this study, we evaluated the potential of a novel synthetic adjuvant designated IC31 for the ability to augment the immune response and protective efficacy of the well-known mycobacterial vaccine antigen, Ag85B-ESAT-6. The IC31 adjuvant, consisting of a vehicle based on the cationic peptide KLKL(5)KLK and the immunostimulatory oligodeoxynucleotide ODN1a signalling through the TLR9 receptor, was found to promote highly efficient Th1 responses. The combination of Ag85B-ESAT-6 and IC31 exhibited significant levels of protection in the mouse aerosol challenge model of tuberculosis and a detailed analysis of the immune response generated revealed the induction of CD4 T cells giving rise to high levels of IFN-gamma secretion. Furthermore, the combination of Ag85B-ESAT-6/IC31 was found to confer efficient protection in the guinea pig aerosol model of tuberculosis infection and is at present moving towards clinical testing.
Agger
Else Marie
EM
Department of Infectious Disease Immunology, Statens Serum Institut, Adjuvant Research, 5 Artillerivej, DK-2300 Copenhagen S, Denmark. eag@ssi.dk
Rosenkrands
Ida
I
Olsen
Anja Weinreich
AW
Hatch
Graham
G
Williams
Ann
A
Kritsch
Constantia
C
Lingnau
Karen
K
von Gabain
Alexander
A
Andersen
Claire Swetman
CS
Korsholm
Karen Smith
KS
Andersen
Peter
P