Lipopolysaccharide, Lipid A, and Liposomes Containing Lipid A as ImmunologicAdjuvants

摘要

Numerous studies have demonstrated that most or all of the potent adjuvantactivity of Gram-negative bacterial endotoxin resides in the lipid A moiety of lipopolysaccharide (LPS) Synthetic analogues of lipid A have provided insights into structure-activity relationships. Several cellular mechanisms of LPS and lipid A adjuvant activities have been identified. Activation of macrophages by LPS or lipid A results in cytokine secretions that enhance the immune response. LPS and lipid A cause recruitment of antigen-presenting cells, particularly macrophages. Liposomes containing lipid A serve as an in vivo adjuvant to recruit increased number of macrophages. Liposomal lipid A that has been phagozytized by cultured macrophages also serves as an intracellular adjuvant to cause increased immunologic presentation of liposomal antigen by the macrophages to specific T lymphocytes, Lipid A can abolish suppressor T cell activity, resulting in increased immune responses to polysaccharide antigens. Upon combination of lipid A or lipid A analogues with nonionic block polymers, modulation of murine antibody isotypes can be achieved with antibodies against a variety of antigens in vivo.