Richards R L, Alving C R, Wassef N M
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
J Pharm Sci. 1996 Dec;85(12):1286-9. doi: 10.1021/js9601593.
Protein and peptide antigens frequently are only slightly immunogenic when utilized alone in vaccines. Formulation of these antigens in a carrier vehicle, particularly when an adjuvant is included, often results in markedly enhanced immune responses. Encapsulation of peptide and protein antigens in liposomes generally results in a relatively slight enhancement of antibody production compared with that observed with the antigen alone. However, when lipid A is included in the liposomes, immunogenicity is markedly increased compared both with antigen alone and with antigen encapsulated in liposomes lacking lipid A. The enhancement of the immune response caused by lipid A is dependent on the liposomal lipid A dose. Aluminum salts, such as aluminum hydroxide and aluminum phosphate, act as adjuvants for some antigens and are used in a variety of human vaccines. When liposomes containing encapsulated protein or peptide antigens were adsorbed with aluminum hydroxide, an enhancement of the antibody response was observed with some antigens, whereas with other antigens the presence of aluminum hydroxide either had no effect or resulted in a diminished antibody response. Immunogenicity of protein and peptide antigens can be enhanced by formulation in liposomes containing lipid A and, depending on the antigen, can be enhanced further by adsorption of the liposomal antigen formulation with aluminum salts.
蛋白质和肽抗原单独用于疫苗时,免疫原性通常较弱。将这些抗原与载体一起配制,尤其是加入佐剂时,往往会显著增强免疫反应。与单独使用抗原相比,将肽和蛋白质抗原包裹在脂质体中通常只会使抗体产生略有增强。然而,当脂质体中含有脂质A时,与单独使用抗原以及不含脂质A的脂质体包裹抗原相比,免疫原性会显著增加。脂质A引起的免疫反应增强取决于脂质体脂质A的剂量。铝盐,如氢氧化铝和磷酸铝,可作为某些抗原的佐剂,并用于多种人类疫苗中。当含有包裹蛋白质或肽抗原的脂质体与氢氧化铝吸附时,某些抗原的抗体反应增强,而对于其他抗原,氢氧化铝的存在要么没有影响,要么导致抗体反应减弱。蛋白质和肽抗原的免疫原性可通过与含有脂质A的脂质体一起配制来增强,并且根据抗原不同,脂质体抗原制剂与铝盐吸附可进一步增强免疫原性。