Enhancement of immunogenicity of tumour virus antigen by liposomes: the effect of lipid composition

Abstract

The secondary humoral response evoked in W/Fu rats by the weakly immunogenic soluble Gross cell surface antigen (GCSAa) extracted from the syngeneic (C58NT)D lymphoma can be enhanced when GCSAa is presented in liposomes, and this requires the antigen to be strongly associated with the phospholipid bilayers. In order to investigate further the role of the phospholipid microenvironment in the membrane presentation of this antigen, the relationship between the phospholipid composition and the immunogenic potency of GCSAa liposomes was explored. For a given neutral phospholipid component, optimal immunogenicity was obtained when 20% cholesterol was present and when a negatively charged phospholipid was included as a minor component. When phosphatidylcholines (PC) were used as the major neutral component, the immunogenicity of GCSAa liposomes from optimal for distearoyl PC (DSPC) decreased when decreasing the PC acyl chain length down to the background level for dilauroyl PC (DLPC). Similarly, the use of PC with acyl chain of increasing unsaturation was followed by a decline in the immunogenicity of the GCSAa liposomes up to the background level for dilinoleoyl PC (DLiPC). Replacing PC headgroups by phosphatidylethanolamine (PE) headgroups abolished the enhancing effect of the liposome presentation on GCSAa immunogenicity. Three groups of phospholipids unable to promote the expression of the GCSAa immunogenicity could be distinguished: the DLPC, DLiPC group, unable to prime the animals but, contrary to the soluble antigen, able to boost the animal after an appropriate priming with GCSAa-DSPC-liposomes, the dimyristoyl PE group, unable to prime or to boost and non-toxic in vitro for the macrophages, and the dipalmitoyl PE group, acutely toxic for macrophages.