The goal of our research is to use subunit peptide antigens as a means of inducing effective antiviral immunity. We hypothesize that liposomes containing optimal combinations of peptides which stimulate both T helper cells as well as specific B cells when administered to nontoxic synthetic adjuvants will be highly immunogenic and will induce protective immunity. Well characterized herpes simplex virus (HSV) test systems will be used to measure protective immunity in vivo. To facilitate liposome incorporation and to enhance immunogenicity, peptides will be derivitized with palmitic acid residues and the lipid soluble synthetic adjuvant muramyl tripeptide phosphatidylethanolamine (MTP-PE) will be used. The relative merits of helper T cell determinants taken from homologous HSV proteins (cognate help) versus helper peptides from other sources (noncognate help) will be evaluated. A second line of investigation will seek means of eliciting cytotoxic T lymphocytes (CTL) with exogenous proteins and peptides. Liposomes constructed so as to disrupt under mild acid conditions will be used as the antigen carriers since we hypothesize that this approach will avoid delivery to the endosome-lysosome cellular compartment and result in a cytoplasmic location appropriate for processing for CTL recognition. Our experiments should generate basic information useful for the design of antiviral vaccines composed of peptides that are effective against many viral pathogens including the human immunodeficiency virus.
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