Doctoral Dissertations

Date of Award

8-1992

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Microbiology

Major Professor

Barry T. Rouse

Committee Members

Al Ichiki, Erby Wilkinson, Robert Moore

Abstract

Exogenous antigens are normally endocytosed and enter the class II pathway of processing and presentation. It had been shown earlier that soluble antigen could be introduced into the class I pathway of processing and presentation by osmotic loading. It was demonstrated that ovalbumin (OVA) -containing liposomes that destabilize on exposure to low pH, referred to as pH-sensitive liposomes, could sensitize target cells to lysis by class I major histocompatibility complex (MHC) -restricted OVA-specific cytotoxic T lymphocyte (CTL). However, OVA-containing pH-insensitive liposomes, native OVA, or OVA subjected to the same protocol as was used to make the liposomes, failed to sensitize targets to OVA-specific CTL lysis. The pH-sensitive liposomal approach was less toxic and more efficient (about 20-fold) in delivering antigen than the osmotic loading approach.

The in vivo induction of a CTL response usually requires that antigen be endogenously synthesized so that appropriate processing can occur. In most of the few examples where successful CTL induction was reported with proteins and peptides, unacceptable adjuvants or means of antigen formulations were used. In the present study, liposomes were used to incorporate the soluble proteins OVA and βgalactosidase. This simple and convenient to use approach, which requires minimal amounts of antigen, resulted in the priming of a CD8+ CTL response and the establishment of immunologic memory. The liposome approach was also extended to include gB protein of herpes simplex virus. Although, no CTL induction was observed, an antibody as well as a proliferative immune response was generated.

Download
Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Share

COinS