Epitopes described in "Protection against lethal vaccinia virus challenge in HLA-A2 transgenic mice by immunization with a single CD8+ T-cell peptide epitope of vaccinia and variola viruses."

Article Authors:James T Snyder; Igor M Belyakov; Amiran Dzutsev; François Lemonnier; Jay A Berzofsky
Article Title:Protection against lethal vaccinia virus challenge in HLA-A2 transgenic mice by immunization with a single CD8+ T-cell peptide epitope of vaccinia and variola viruses.
Reference Detail
Reference ID:1368
Abstract:CD8(+) T lymphocytes have been shown to be involved in controlling poxvirus infection, but no protective cytotoxic T-lymphocyte (CTL) epitopes are defined for variola virus, the causative agent of smallpox, or for vaccinia virus. Of several peptides in vaccinia virus predicted to bind HLA-A2.1, three, VETFsm(498-506), A26L(6-14), and HRP2(74-82), were found to bind HLA-A2.1. Splenocytes from HLA-A2.1 transgenic mice immunized with vaccinia virus responded only to HRP2(74-82) at 1 week and to all three epitopes by ex vivo enzyme-linked immunosorbent spot (ELISPOT) assay at 4 weeks postimmunization. To determine if these epitopes could elicit a protective CD8(+) T-cell response, we challenged peptide-immunized HLA-A2.1 transgenic mice intranasally with a lethal dose of the WR strain of vaccinia virus. HRP2(74-82) peptide-immunized mice recovered from infection, while naïve mice died. Depletion of CD8(+) T cells eliminated protection. Protection of HHD-2 mice, lacking mouse class I major histocompatibility complex molecules, implicates CTLs restricted by human HLA-A2.1 as mediators of protection. These results suggest that HRP2(74-82), which is shared between vaccinia and variola viruses, may be a CD8(+) T-cell epitope of vaccinia virus that will provide cross-protection against smallpox in HLA-A2.1-positive individuals, representing almost half the population.
Affiliations:Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1578, USA.
Reference Type:Literature
PubMed ID:15194781
Journal:J Virol
Journal Volume:78
Article Pages:7052-60
Journal ISSN:1098-5514
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@4e59411b;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@45c17bcc;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@21a6b1db;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@46e6b21f;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@53b83596
Article MeSH List:Amino Acid Sequence; Animals; CD8-Positive T-Lymphocytes(immunology); Cell Line; Epitopes, T-Lymphocyte(immunology); HLA-A2 Antigen(genetics); Humans; Immunodominant Epitopes; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peptides(chemistry; immunology); Smallpox(immunology; prevention & control); Smallpox Vaccine(administration & dosage; immunology); Vaccination; Vaccinia virus(immunology; pathogenicity); Variola virus(immunology)
Curation Last Updated:2015-01-17 20:58:27