TLR4 agonists as immunomodulatory agents.
J Endotoxin Res
; 12(5): 313-9, 2006.
Article
en En
| MEDLINE
| ID: mdl-17059695
ABSTRACT
Monophosphoryl lipid A (MPL) is a potent vaccine adjuvant derived from Salmonella minnesota that was recently licensed in Europe as a component of an improved vaccine for hepatitis B (Fendrix). MPL, like lipopolysaccharide from which it is derived, signals via the TLR4/MD-2 complex. We have produced a series of synthetic Toll-like receptor 4 (TLR4) agonists that are based upon the structure of the major hexa-acylated congener contained within MPL. These TLR4 agonists, termed the aminoalkyl glucosaminide phosphates (AGPs), stimulate the production of various cytokines by human peripheral blood mononuclear cells in vitro and up-regulate cell surface markers on monocytes, NK cells and B cells. In addition, AGPs provide non-specific resistance to challenge with viral and bacterial pathogens when administered to the upper airways of mice. Structure-activity relationship studies have shown that the activation of innate immune effectors by AGPs depends primarily on the length of the secondary acyl chains and the nature of the functional group attached to the aglycon component. Moreover, AGPs can act as potent adjuvants for mucosal administration of vaccine antigens, enhancing both antigen-specific antibody and cell-mediated immune responses. Thus, by combining the adjuvant and non-specific resistance induction properties of AGPs it may be possible to generate mucosal vaccines that provide innate protection immediately following administration together with long-term acquired immunity.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Adyuvantes Inmunológicos
/
Receptor Toll-Like 4
/
Factores Inmunológicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Endotoxin Res
Asunto de la revista:
ANGIOLOGIA
/
BACTERIOLOGIA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos