de Haan A, Geerligs H J, Huchshorn J P, van Scharrenburg G J, Palache A M, Wilschut J
Department of Physiological Chemistry, Groningen Institute for Drug Studies, University of Groningen, The Netherlands.
Vaccine. 1995 Feb;13(2):155-62. doi: 10.1016/0264-410x(95)93129-w.
This paper reports on a novel immunoadjuvant activity of liposomes. An influenza subunit preparation, containing the isolated viral surface antigens, was incorporated in a liposomal formulation. Administration of this vaccine to mice via the intranasal (i.n.) route resulted in a stimulated serum IgG response relative to the response to i.n. immunization with the antigen alone. In addition, the liposomal vaccine induced a secretory IgA (sIgA) response in the mucosa of the lungs and nasal cavity. Both serum IgG and sIgA responses persisted up to at least 21 weeks postimmunization. Immune stimulation was observed with negatively charged liposomes consisting of phosphatidylcholine (PC), cholesterol and dicetylphosphate (DCP), but not with zwitterionic liposomes, consisting of PC and cholesterol alone. Remarkably, for stimulation of serum IgG responses and induction of an sIgA response, liposomes could be simply mixed with the antigen. Moreover, i.n. administration of empty liposomes up to 48 h prior to i.n. immunization with the subunit antigen also resulted in immune stimulation, indicating that the liposomes did not exert their adjuvant effect by acting as a carrier for the antigen. The liposomal vaccine conferred protection against infection. It is concluded that liposomes, administered i.n., provide a promising adjuvant system for stimulation of antibody responses in general, and mucosal sIgA responses in particular.
本文报道了脂质体一种新的免疫佐剂活性。一种含有分离出的病毒表面抗原的流感亚单位制剂被包裹在脂质体制剂中。通过鼻内(i.n.)途径给小鼠接种这种疫苗,相对于单独用抗原进行鼻内免疫的反应,可刺激血清IgG反应。此外,脂质体疫苗可在肺和鼻腔黏膜诱导分泌型IgA(sIgA)反应。血清IgG和sIgA反应在免疫后至少持续21周。观察到由磷脂酰胆碱(PC)、胆固醇和磷酸二鲸蜡酯(DCP)组成的带负电荷的脂质体具有免疫刺激作用,而仅由PC和胆固醇组成的两性离子脂质体则没有这种作用。值得注意的是,为了刺激血清IgG反应和诱导sIgA反应,脂质体可简单地与抗原混合。此外,在鼻内用亚单位抗原免疫前48小时内鼻内给予空脂质体也会导致免疫刺激,这表明脂质体并非通过作为抗原载体发挥其佐剂作用。脂质体疫苗可提供抗感染保护。得出的结论是,经鼻内给药的脂质体总体上为刺激抗体反应,尤其是黏膜sIgA反应提供了一种有前景的佐剂系统。