Epitopes described in "A novel HLA (HLA-A*0201) transgenic rabbit model for preclinical evaluation of human CD8+ T cell epitope-based vaccines against ocular herpes."

Article Authors:Aziz A Chentoufi; Gargi Dasgupta; Neil D Christensen; Jiafen Hu; Zareen S Choudhury; Arfan Azeem; James V Jester; Anthony B Nesburn; Steven L Wechsler; Lbachir BenMohamed
Article Title:A novel HLA (HLA-A*0201) transgenic rabbit model for preclinical evaluation of human CD8+ T cell epitope-based vaccines against ocular herpes.
Reference Detail
Reference ID:1019097
Abstract:We introduced a novel humanized HLA-A*0201 transgenic (HLA Tg) rabbit model to assess the protective efficacy of a human CD8(+) T cell epitope-based vaccine against primary ocular herpes infection and disease. Each of the three immunodominant human CD8(+) T cell peptide epitopes from HSV-1 glycoprotein D (gD(53-61), gD(70-78), and gD(278-286)) were joined with a promiscuous human CD4(+) T cell peptide epitope (gD(49-82)) to construct three separate pairs of CD4-CD8 peptides. Each CD4-CD8 peptide pair was then covalently linked to an N(epsilon)-palmitoyl-lysine residue via a functional base lysine amino group to construct CD4-CD8 lipopeptides. HLA Tg rabbits were immunized s.c. with a mixture of the three CD4-CD8 HSV-1 gD lipopeptides. The HSV-gD-specific T cell responses induced by the mixture of CD4-CD8 lipopeptide vaccine and the protective efficacy against acute virus replication and ocular disease were determined. Immunization induced HSV-gD(49-82)-specific CD4(+) T cells in draining lymph node (DLN); induced HLA-restricted HSV-gD(53-61), gD(70-78), and gD(278-286)-specific CD8(+) T cells in DLN, conjunctiva, and trigeminal ganglia and reduced HSV-1 replication in tears and corneal eye disease after ocular HSV-1 challenge. In addition, the HSV-1 epitope-specific CD8(+) T cells induced in DLNs, conjunctiva, and the trigeminal ganglia were inversely proportional with corneal disease. The humanized HLA Tg rabbits appeared to be a useful preclinical animal model for investigating the immunogenicity and protective efficacy of human CD8(+) T cell epitope-based prophylactic vaccines against ocular herpes. The relevance of HLA Tg rabbits for future investigation of human CD4-CD8 epitope-based therapeutic vaccines against recurrent HSV-1 is discussed.
Affiliations:Laboratory of Cellular and Molecular Immunology, The Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA.
Reference Type:Literature
PubMed ID:20124097
Journal:J Immunol
Journal Volume:184
Article Pages:2561-71
Journal ISSN:0022-1767
Article Chemical List:Epitopes, T-Lymphocyte;HLA-A Antigens;HLA-A*02:01 antigen;HLA-A2 Antigen;Herpes Simplex Virus Vaccines;N(epsilon)-palmitoyllysine;Peptide Fragments;Viral Envelope Proteins;glycoprotein D, Human herpesvirus 1;Lysine
Article MeSH List:Amino Acid Sequence; Animals; Animals, Genetically Modified; CD4-Positive T-Lymphocytes(immunology; metabolism); CD8-Positive T-Lymphocytes(immunology; metabolism); Conjunctiva(immunology; metabolism; virology); Cornea(immunology; metabolism; virology); Epitopes, T-Lymphocyte(chemistry; genetics; immunology); HLA-A Antigens(genetics; immunology); HLA-A2 Antigen; Herpes Simplex Virus Vaccines(administration & dosage; genetics; immunology); Herpesvirus 1, Human(immunology); Humans; Immunization; Keratitis, Herpetic(immunology; prevention & control; virology); Lymph Nodes(immunology; metabolism; virology); Lysine(analogs & derivatives; chemistry); Molecular Sequence Data; Peptide Fragments(chemistry; genetics; immunology); Rabbits; Trigeminal Ganglion(immunology; metabolism; virology); Viral Envelope Proteins(chemistry; genetics; immunology)
Curation Last Updated:2016-04-11 21:09:19