Novel generation mycobacterial adjuvant based on liposome-encapsulated monomycoloyl glycerol from Mycobacterium bovis bacillus Calmette-Guérin.
The immunostimulatory activity of lipids associated with the mycobacterial cell wall has been recognized for several decades and exploited in a large variety of different adjuvant preparations. Previously, we have shown that a mycobacterial lipid extract from Mycobacterium bovis bacillus Calmette-Guérin delivered in cationic liposomes was a particular efficient Th1-inducing adjuvant formulation effective against tuberculosis. Herein, we have dissected the adjuvant activity of the bacillus Calmette-Guérin lipid extract showing that the majority of the activity was attributable to the apolar lipids and more specifically to a single lipid, monomycoloyl glycerol (MMG), previously also shown to stimulate human dendritic cells. Delivered in cationic liposomes, MMG induced the most prominent Th1-biased immune response that provided significant protection against tuberculosis. Importantly, a simple synthetic analog of MMG, based on a 32 carbon mycolic acid, was found to give rise to comparable high Th1-biased responses with a major representation of polyfunctional CD4 T cells coexpressing IFN-gamma, TNF-alpha, and IL-2. Furthermore, comparable activity was shown by an even simpler monoacyl glycerol analog, based on octadecanoic acid. The use of these synthetic analogs of MMG represents a promising new strategy for exploiting the immunostimulatory activity and adjuvant potential of components from the mycobacterial cell wall without the associated toxicity issues observed with complex mycobacterial preparations.
Andersen
Claire A Swetman
CA
Department of Infectious Disease Immunology, Adjuvant Research, Statens Serum Institut, Copenhagen, Denmark;
Rosenkrands
Ida
I
Olsen
Anja W
AW
Nordly
Pernille
P
Christensen
Dennis
D
Lang
Roland
R
Kirschning
Carsten
C
Gomes
Jessica M
JM
Bhowruth
Veemal
V
Minnikin
David E
DE
Besra
Gurdyal S
GS
Follmann
Frank
F
Andersen
Peter
P
Agger
Else Marie
EM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005990:Glycerol / Q000008:administration & dosage / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050178:Monoglycerides / Q000008:administration & dosage* / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology*; D009171:Mycolic Acids / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D008081:Liposomes; D050178:Monoglycerides; D009171:Mycolic Acids; C543328:monomycoloyl glycerol; D005990:Glycerol