Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Virol. 2010 Oct;84(19):9947-56. doi: 10.1128/JVI.00672-10. Epub 2010 Jul 28.

A multivalent vaccination strategy for the prevention of Old World arenavirus infection in humans.

Author information

  • 1Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA. jbotten@uvm.edu

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 [GPC(441-449)]), LCMV (GPC(447-455)), JUNV (GPC(429-437)), MACV (GPC(444-452)), GTOV (GPC(427-435)), and WWAV (GPC(428-436)) 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 GPC(441-449) or LCMV GPC(447-455) induced high-avidity CD8(+) T-cell responses that were able to kill syngeneic target cells pulsed with either LASV GPC(441-449) or LCMV GPC(447-455) 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.

PMID:
20668086
[PubMed - indexed for MEDLINE]
PMCID:
PMC2937778
Free PMC Article

Images from this publication.See all images (5)Free text

FIG. 1.
FIG. 2.
FIG. 3.
FIG. 4.
FIG. 5.

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Write to the Help Desk