Chimeric calicivirus-like particles elicit protective anti-viral cytotoxic responses without adjuvant

Virology. 2009 May 10;387(2):303-12. doi: 10.1016/j.virol.2009.02.045. Epub 2009 Mar 26.

Abstract

We have analyzed the potential of virus-like particles (VLPs) from rabbit hemorrhagic disease virus (RHDV) as a delivery system for foreign T cell epitopes. To accomplish this goal, we generated chimeric RHDV-VLPs incorporating a CD8(+) T cell epitope (SIINFEKL) derived from chicken ovalbumin (OVA). The OVA epitope was inserted in the capsid protein (VP60) of RHDV at two different locations: 1) the N-terminus, predicted to be facing to the inner core of the VLPs, and 2) a novel insertion site predicted to be located within an exposed loop. Both constructions correctly assembled into VLPs. In vitro, the chimeric VLPs activated dendritic cells for TNF-alpha secretion and they were processed and presented to specific T cells. In vivo, mice immunized with the chimeric VLPs without adjuvant were able to induce specific cellular responses mediated by cytotoxic and memory T cells. More importantly, immunization with chimeric VLPs was able to resolve an infection by a recombinant vaccinia virus expressing OVA protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Caliciviridae Infections / immunology*
  • Chickens
  • Cytotoxicity Tests, Immunologic
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / metabolism
  • Female
  • Hemorrhagic Disease Virus, Rabbit / genetics
  • Hemorrhagic Disease Virus, Rabbit / immunology*
  • Immunologic Memory
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Reassortant Viruses / immunology
  • Reassortant Viruses / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccination
  • Vaccinia / prevention & control*
  • Vaccinia / virology
  • Vaccinia virus / genetics
  • Vaccinia virus / isolation & purification
  • Viral Vaccines / immunology*
  • Virion / immunology
  • Virion / metabolism

Substances

  • Adjuvants, Immunologic
  • Epitopes, T-Lymphocyte
  • Viral Vaccines
  • Ovalbumin