In silico-accelerated identification of conserved and immunogenic variola/vaccinia T-cell epitopes

TY - JOUR

T1 - In silico-accelerated identification of conserved and immunogenic variola/vaccinia T-cell epitopes

AU - Moise, Leonard

AU - McMurry, Julie A

AU - Buus, Søren

AU - Frey, Sharon

AU - Martin, William D

AU - De Groot, Anne S

N1 - Keywords: Adult; Computational Biology; Cross Reactions; Epitope Mapping; Epitopes, T-Lymphocyte; Genes, MHC Class I; Genes, MHC Class II; Genome, Viral; Humans; Open Reading Frames; Smallpox Vaccine; T-Lymphocytes; Vaccinia virus; Variola virus; Young Adult

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1016/j.vaccine.2009.06.018

DO - 10.1016/j.vaccine.2009.06.018

M3 - Journal article

C2 - 19559119

SN - 0264-410X

VL - 27

SP - 6471

EP - 6479

JO - Vaccine

JF - Vaccine

IS - 46

ER -