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A.B. Nesburn, X. Zhang, A. Issagholian, X. Zhu, L. BenMohamed; Induction of CD8 T–Cell–Specific Immunity Against Ocular Herpes Simplex Virus With a Th–CTL Fusion Synthetic Lipopeptide: The Lipid Moiety Units Influence Priming for Protective CD8+ Cytotoxic T Lymphocytes . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2787.
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© ARVO (1962-2015); The Authors (2016-present)
Ocular infection, caused by herpes simplex virus type 1 (HSV–1), is a significant public health problem worldwide. Among the challenges that face the development of a vaccine strategy against ocular herpes is the requirement for an effective and safe immunization regimen. Purpose: The ultimate aim of our studies is to develop an antigen–specific and lipopeptide–based immunogenic strategy against ocular HSV–1. Methods: Toward this end, we have investigated the influence of the number of lipid units on the immunogenicity of lipopeptides. We constructed a model fusion lipopeptide vaccine that contained the HSV–1 immunodominant Kb–restricted gB498–505 CD8(+) CTL epitope synthesized in tandem with the Pan DR helper CD4(+) T cell epitope (PADRE) which binds most common HLA–DR molecules with high affinity. The peptide backbone was then covalently linked with either one (1PAM), two (2PAM), or three (3PAM) N–epsilon–palmitoyl–lysines. The immunogenicity and protective efficacy of these molecularly defined antigenic formulations, delivered subcutaneously in the absence of exogenous adjuvants, were evaluated following ocular HSV–1 (McKrae) challenge of C57BL/6 (H2b) mice. The ability of the fusion synthetic lipopeptide to induce gB498–505–specific CD8(+) T cells was determined ex–vivo by CD8+ tetramer assay and in vitro by cytotoxicity and IFN–γ ELISpot assays. Results:The frequency and magnitude of gB498–505–specific CD8(+) T cells that were induced correlated with the number of the lipids units. Immunization with the 3PAM lipopeptide generated the highest frequency of CD8(+) T cells. HSV–1–induced blepharitis and corneal scarring were reduced, with the highest protection occurring in 3PAM lipopeptide immunized mice. Conclusions: These results highlight the potential of T cell epitope based lipopeptide vaccines as painless, safe, and non–invasive immunogenic formulations.
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