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

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

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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 (gD53-61, gD70-78, and gD 278-286) were joined with a promiscuous human CD4+ T cell peptide epitope (gD49-82) to construct three separate pairs of CD4-CD8 peptides. Each CD4-CD8 peptide pair was then covalently linked to an Nε-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-gD49-82-specific CD4+ T cells in draining lymph node (DLN); induced HLA-restricted HSV-gD 53-61, gD70-78, and gD278-286-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.

Original languageEnglish (US)
Pages (from-to)2561-2571
Number of pages11
JournalJournal of Immunology
Volume184
Issue number5
DOIs
StatePublished - Mar 1 2010

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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