title: "HIV-peplotion vaccine"--a novel approach to protection against AIDS by transepithelial transport of viral peptides to Langerhans cells for long-term antiviral CTL response. (A review).
abstract: Viral vaccines which stimulate the humoral immune response in humans have been successful in preventing most of the known virus diseases except dengue fever, respiratory syncytial virus infections and HIV-1-related AIDS. Burke [1] raised a concern that anti-HIV-1 antibodies may add a risk factor to immunized individuals infected with HIV-1. An approach to develop HIV-1 vaccines capable of stimulating anti-HIV-1 cytotoxic T cells requires an understanding of the importance of epidermal and epithelial Langerhans cells (LC). These cells are professional antigen-presenting cells which express HLA class I and class II molecules. Epithelial LC are present in a specific layer in the skin, genitalia and gut and may be accessible to viral antigens by local application in a vehicle for transepithelial transport of viral proteins/peptides (designated "HIV-1 Peplotion vaccine"). This approach is supported by the reports that HIV-1 gp160 in ISCOM induced MHC class I CTL response [2], mixing of cationic lipids with viral proteins formed complexes which were delivered to cell cytoplasm and the degraded peptides stimulated CTLs by HLA class I mechanism [3] and viral proteins encapsulated in pH-sensitive liposomes administered to LC induced primary antiviral CTLs [4]. Current studies in our laboratory deal with (a) selection of the vehicle for transepidermal transport of peptides and the conditions for selective uptake by epidermal LC [5]; (b) computer analysis of HIV-1 proteins to detect the putative proteolytic cleavage peptides with amino acid motifs which allow association with different known HLA class I haplotype molecules on LCs and synthetic peptide uptake from "without" by LC. The "HIV-1 Peplotion vaccine", when developed, will be useful for continual stimulation of antiviral CTLs in uninfected individuals and HIV-1 carriers by repetitive application to skin, genitalia and gut. The "Peplotion vaccine" will be applied by vaccinees, will be affordable for all human-populations and, hopefully, will be highly efficient.
authors.affiliation: Department of Molecular Virology, Faculty of Medicine, Hebrew University of Jerusalem, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Becker
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D001692:Biological Transport / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D001330:Electronic Data Processing; D004848:Epithelium / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control*; D015497:HIV-1; D006239:Haplotypes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology / Q000493:pharmacokinetics; D012867:Skin / Q000276:immunology*; D014611:Vaccination; D014764:Viral Proteins / Q000138:chemical synthesis / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides; D014764:Viral Proteins