Vaccination with immunodominant peptides encapsulated in Quil A-containing liposomes induces peptide-specific primary CD8+ cytotoxic T cells

Abstract

Immunostimulating complexes (ISCOMs), containing lipids, the saponin Quil A, and proteinaceous antigens, have been proven to vaccinate effectively CD8+ cytolytic T cells in vivo. However, conventional ISCOM technology is restricted to hydrophobic proteins or fatty acid-derivatized proteins or peptides. We therefore analysed whether Quil A-containing liposomes are an effective vehicle to shuttle hydrophilic proteins or peptides into the MHC class I pathway of antigen presentation resulting in the in vivo induction of antigen-specific cytolytic T cells (CTL). Liposomes were formed by a lipid dry-down method followed by resuspension with an aqueous solution containing protein/peptide and Quil A and then an extrusion step. Quil A-containing liposomes are an effective means to elicit a CD8+ CTL response to peptide antigen in vivo. CTL could be raised in C57B1/6 mice against ovalbumin (OVA) peptide 257–264 and vesicular stomatitis virus nucleoprotein 52–59, as well as in Balb/c mice against listeriolysin peptide 91–99 and cytomegalovirus pp89 168–176, demonstrating the versatility of this approach. The elicited response was peptide-specific, peptide dose-dependent and Quil A was necessary. Vaccination with liposomes entrapping the whole ovalbumin molecule or an extended (OVA) peptide 254–276 also yielded a CTL responsive to the immunodominant OVA peptide 256–264, implying cellular internalization and correct processing. Thus Quil A-containing liposomes appear to be a versatile vehicle to vaccinate CD8+ T cells in vivo; in addition, they could rapidly enhance the understanding of subunit vaccines and rules of antigen processing and peptide-MHC class 1 binding.