Adjuvant activity of emulsan, a secreted lipopolysaccharide from acinetobacter calcoaceticus.
Several promising adjuvant candidates have been studied over the past 75 years; however, only alum is currently approved for human use. The complex acylated polysaccharide emulsan, secreted from Acinetobacter calcoaceticus, represents a new candidate. Unique features of this family of polymers are their amenability to structural tailoring and their emulsification behavior. We demonstrate that emulsan activates macrophages in a dose-dependent manner. This activation is dependent on the presence of the fatty acid side chains that decorate the polysaccharide backbone, and, furthermore, the level of activation can be affected by changes in the chemical characteristics of emulsan structural variants. One emulsan variant was examined in a classical hapten carrier immunization protocol and demonstrated significant adjuvant activity as determined by hapten-specific antibody titers. This immune response was characterized by a high immunoglobulin G2a titer, consistent with a Th1 response. The significant immunopotentiation demonstrated by this complex polymer establishes emulsan as an exciting new candidate adjuvant. Furthermore, by manipulating the chemical structure of this compound, we can explore the physical basis of pattern recognition receptors and macrophage activation.
Panilaitis
Bruce
B
Department of Biology,Tufts University, Medford, Massachusetts 02155, USA. bpanilai@emerald.tufts.edu
Johri
Atul
A
Blank
Walter
W
Kaplan
David
D
Fuhrman
Juliet
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D005260:Female; D007114:Immunization; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D011135:Polysaccharides, Bacterial; C036028:emulsan