Induction of ebolavirus cross-species immunity using retrovirus-like particles bearing the Ebola virus glycoprotein lacking the mucin-like domain

Virol J. 2012 Jan 25:9:32. doi: 10.1186/1743-422X-9-32.

Abstract

Background: The genus Ebolavirus includes five distinct viruses. Four of these viruses cause hemorrhagic fever in humans. Currently there are no licensed vaccines for any of them; however, several vaccines are under development. Ebola virus envelope glycoprotein (GP1,2) is highly immunogenic, but antibodies frequently arise against its least conserved mucin-like domain (MLD). We hypothesized that immunization with MLD-deleted GP1,2 (GPΔMLD) would induce cross-species immunity by making more conserved regions accessible to the immune system.

Methods: To test this hypothesis, mice were immunized with retrovirus-like particles (retroVLPs) bearing Ebola virus GPΔMLD, DNA plasmids (plasmo-retroVLP) that can produce such retroVLPs in vivo, or plasmo-retroVLP followed by retroVLPs.

Results: Cross-species neutralizing antibody and GP1,2-specific cellular immune responses were successfully induced.

Conclusion: Our findings suggest that GPΔMLD presented through retroVLPs may provide a strategy for development of a vaccine against multiple ebolaviruses. Similar vaccination strategies may be adopted for other viruses whose envelope proteins contain highly variable regions that may mask more conserved domains from the immune system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood*
  • Cross Reactions*
  • Ebola Vaccines / administration & dosage
  • Ebola Vaccines / genetics
  • Ebola Vaccines / immunology*
  • Ebolavirus / immunology*
  • Female
  • Glycoproteins / genetics
  • Glycoproteins / immunology
  • Immunity, Cellular
  • Mice
  • Mice, Inbred BALB C
  • Protein Structure, Tertiary
  • Retroviridae / genetics
  • Retroviridae / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Vaccines, Virosome / administration & dosage
  • Vaccines, Virosome / genetics
  • Vaccines, Virosome / immunology
  • Viral Proteins / genetics
  • Viral Proteins / immunology*
  • Virosomes / genetics
  • Virosomes / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Ebola Vaccines
  • Glycoproteins
  • Vaccines, Synthetic
  • Vaccines, Virosome
  • Viral Proteins
  • Virosomes