In silico-accelerated identification of conserved and immunogenic variola/vaccinia T-cell epitopes.
Epitopes shared by the vaccinia and variola viruses underlie the protective effect of vaccinia immunization against variola infection. We set out to identify a subset of cross-reactive epitopes using bioinformatics and immunological methods. Putative T-cell epitopes were computationally predicted from highly conserved open reading frames from seven complete vaccinia and variola genomes using EpiMatrix. Over 100 epitopes bearing low human sequence homology were selected and assessed in HLA binding assays and in T-cell antigenicity assays using PBMCs isolated from Dryvax-immunized subjects. This experimental validation of computational predictions illustrates the potential for immunoinformatics methods to identify candidate immunogens for a new, safer smallpox vaccine.
Moise
Leonard
L
EpiVax, Inc., Providence, RI, USA.
McMurry
Julie A
JA
Buus
Soren
S
Frey
Sharon
S
Martin
William D
WD
De Groot
Anne S
AS
D000328:Adult; D019295:Computational Biology; D003429:Cross Reactions; D018604:Epitope Mapping / Q000379:methods*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D016679:Genome, Viral; D006801:Humans; D016366:Open Reading Frames; D012900:Smallpox Vaccine / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D012901:Variola virus / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
C078786:DryVax vaccine; D018984:Epitopes, T-Lymphocyte; D012900:Smallpox Vaccine