title: Induction of ebolavirus cross-species immunity using retrovirus-like particles bearing the Ebola virus glycoprotein lacking the mucin-like domain.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Bldg, 29B, Room 5NN22, 8800 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Wu
authors.initials: W
authors.lastname: Ou
authors.forename: Josie
authors.initials: J
authors.lastname: Delisle
authors.forename: Jerome
authors.initials: J
authors.lastname: Jacques
authors.forename: Joanna
authors.initials: J
authors.lastname: Shih
authors.forename: Graeme
authors.initials: G
authors.lastname: Price
authors.forename: Jens H
authors.initials: JH
authors.lastname: Kuhn
authors.forename: Vivian
authors.initials: V
authors.lastname: Wang
authors.forename: Daniela
authors.initials: D
authors.lastname: Verthelyi
authors.forename: Gerardo
authors.initials: G
authors.lastname: Kaplan
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Wilson
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D003429:Cross Reactions; D046129:Ebola Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D029043:Ebolavirus / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D012190:Retroviridae / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D022701:Virosomes / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D046129:Ebola Vaccines; D006023:Glycoproteins; D014614:Vaccines, Synthetic; D022721:Vaccines, Virosome; D014764:Viral Proteins; D022701:Virosomes