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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI024762-08
Application #
2062733
Study Section
Virology Study Section (VR)
Project Start
1987-06-01
Project End
1995-05-31
Budget Start
1994-06-01
Budget End
1995-05-31
Support Year
8
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Tennessee Knoxville
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
City
Knoxville
State
TN
Country
United States
Zip Code
37996
Babu, J S; Nair, S; Kanda, P et al. (1995) Priming for virus-specific CD8+ but not CD4+ cytotoxic T lymphocytes with synthetic lipopeptide is influenced by acylation units and liposome encapsulation. Vaccine 13:1669-76
Nair, S; Buiting, A M; Rouse, R J et al. (1995) Role of macrophages and dendritic cells in primary cytotoxic T lymphocyte responses. Int Immunol 7:679-88
Rouse, R J; Nair, S K; Lydy, S L et al. (1994) Induction in vitro of primary cytotoxic T-lymphocyte responses with DNA encoding herpes simplex virus proteins. J Virol 68:5685-9
Zhou, F; Huang, L (1994) Liposome-mediated cytoplasmic delivery of proteins: an effective means of accessing the MHC class I-restricted antigen presentation pathway. Immunomethods 4:229-35
Banks, T A; Jenkins, F J; Kanangat, S et al. (1994) Vaccination with the immediate-early protein ICP47 of herpes simplex virus-type 1 (HSV-1) induces virus-specific lymphoproliferation, but fails to protect against lethal challenge. Virology 200:236-45
Martin, S; Mercadal, C M; Weir, J P et al. (1993) The proportion of herpes simplex virus-specific cytotoxic T lymphocytes (Tc) that recognize glycoprotein C varies between individual mice and is dependent on the form of immunization. Viral Immunol 6:21-33
Banks, T A; Nair, S; Rouse, B T (1993) Recognition by and in vitro induction of cytotoxic T lymphocytes against predicted epitopes of the immediate-early protein ICP27 of herpes simplex virus. J Virol 67:613-6
Nair, S; Babu, J S; Dunham, R G et al. (1993) Induction of primary, antiviral cytotoxic, and proliferative responses with antigens administered via dendritic cells. J Virol 67:4062-9
Zhou, F; Rouse, B T; Huang, L (1992) Induction of cytotoxic T lymphocytes in vivo with protein antigen entrapped in membranous vehicles. J Immunol 149:1599-604
Nair, S; Zhou, F; Reddy, R et al. (1992) Soluble proteins delivered to dendritic cells via pH-sensitive liposomes induce primary cytotoxic T lymphocyte responses in vitro. J Exp Med 175:609-12

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