Showing papers by "Jason K. Whitmire published in 2010"
TL;DR: It is demonstrated that HLA class I-restricted, cross-reactive epitopes exist among diverse arenaviruses and that individual epitopes can be utilized as effective vaccine determinants for multiple pathogenic arenavIRuses.
Abstract: Arenaviruses cause severe human disease ranging from aseptic meningitis following lymphocytic choriomeningitis virus (LCMV) infection to hemorrhagic fever syndromes following infection with Guanarito virus (GTOV), Junin virus (JUNV), Lassa virus (LASV), Machupo virus (MACV), Sabia virus (SABV), or Whitewater Arroyo virus (WWAV). Cellular immunity, chiefly the CD8 T-cell response, plays a critical role in providing protective immunity following infection with the Old World arenaviruses LASV and LCMV. In the current study, we evaluated whether HLA class I-restricted epitopes that are cross-reactive among pathogenic arenaviruses could be identified for the purpose of developing an epitope-based vaccination approach that would cross-protect against multiple arenaviruses. We were able to identify a panel of HLA-A*0201-restricted peptides derived from the same region of the glycoprotein precursor (GPC) of LASV (GPC spanning residues 441 to 449 [GPC441-449]), LCMV (GPC447-455), JUNV (GPC429-437), MACV (GPC444-452), GTOV (GPC427-435), and WWAV (GPC428-436) that displayed high-affinity binding to HLA-A*0201 and were recognized by CD8 T cells in a cross-reactive manner following LCMV infection or peptide immunization of HLA-A*0201 transgenic mice. Immunization of HLA-A*0201 mice with the Old World peptide LASV GPC441-449 or LCMV GPC447-455 induced high-avidity CD8 T-cell responses that were able to kill syngeneic target cells pulsed with either LASV GPC441-449 or LCMV GPC447-455 in vivo and provided significant protection against viral challenge with LCMV. Through this study, we have demonstrated that HLA class I-restricted, cross-reactive epitopes exist among diverse arenaviruses and that individual epitopes can be utilized as effective vaccine determinants for multiple pathogenic arenaviruses. Arenaviruses are a family of rodent-borne viruses that are associated with severe disease in humans. Phylogenetically, the arenaviruses are organized into Old World or New World groups, with a subdivision of the New World viruses falling into three distinct lineages (A to C) (17). At least eight arenaviruses are known to cause human disease. Of the New World viruses, Junin virus (JUNV), Machupo virus (MACV), Guanarito virus (GTOV), and Sabia virus (SABV) (all members of lineage B) are etiologic agents of hemorrhagic fever syndromes in South
25 citations