Influence of peptide acylation, liposome incorporation and synthetic immunomodulators on the immunogenicity of herpes simplex virus glycoprotein D peptides : implications for subunit vaccines

Author

Ketil Brynestad

Date of Award

5-1991

Degree Type

Thesis

Degree Name

Master of Science

Major

Microbiology

Major Professor

Barry T. Rouse

Committee Members

Robert Moore, Alex Osmand

Abstract

The goal for the development of a synthetic vaccine for herpes simplex viruses is a chemically defined, safe, and effective formulation containing relevant B and T cell epitopes without a macromolecular carrier. Such a synthetic vaccine would eliminate the irrelevant determinants of the virus that may cause undesirable side effects. In this study, a peptide corresponding to amino acid residues 1-23 of glycoprotein D of herpes simplex virus type 1 was chemically synthesized and coupled to a fatty acid carrier by standard Merrifield synthesis procedures. The resulting peptide-palmitic acid conjugate (acylpeptide) exhibited enhanced immunogenicity in mice as compared to that exhibited by the free form of the peptide. When the the acylpeptide was incorporated into liposomes the immunogenicity of the peptide was further increased. Inclusion of the immunomodulators muramyl tripeptide phosphatidlyethanolamine and monophosphoryl lipid A into the same liposome stimulated the strongest immune response. The humoral immune responses induced by the acylpeptide-liposome construct were greater than those induced by peptide in Freund complete adjuvant, and cellular responses were equivalent. The acylpeptide-immunomodulator- liposome formulation also induced significant levels of protective immunity. although the immunity was less than that induced by herpes simplex virus infection. Acylated peptides, especially in liposomes, were taken up more effectively by draining lymph nodes, which possibly explains in part the enhanced immunogenicity of the peptides. Since the acylpeptide- immunoliposome formulation used was nontoxic, it represents a useful way to enhance immunogenicity of subunit peptides used for vaccine purposes in humans and animals.

Recommended Citation

Brynestad, Ketil, "Influence of peptide acylation, liposome incorporation and synthetic immunomodulators on the immunogenicity of herpes simplex virus glycoprotein D peptides : implications for subunit vaccines. " Master's Thesis, University of Tennessee, 1991.
https://trace.tennessee.edu/utk_gradthes/12354