title: A Lentiviral Vector Expressing Japanese Encephalitis Virus-like Particles Elicits Broad Neutralizing Antibody Response in Pigs.
abstract: BACKGROUND
  Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in Southeast Asia. Vaccination of domestic pigs has been suggested as a "one health" strategy to reduce viral disease transmission to humans. The efficiency of two lentiviral TRIP/JEV vectors expressing the JEV envelope prM and E glycoproteins at eliciting protective humoral response was assessed in a mouse model and piglets.
  
  
  RESULTS
  A gene encoding the envelope proteins prM and E from a genotype 3 JEV strain was inserted into a lentiviral TRIP vector. Two lentiviral vectors TRIP/JEV were generated, each expressing the prM signal peptide followed by the prM protein and the E glycoprotein, the latter being expressed either in its native form or lacking its two C-terminal transmembrane domains. In vitro transduction of cells with the TRIP/JEV vector expressing the native prM and E resulted in the efficient secretion of virus-like particles of Japanese encephalitis virus. Immunization of BALB/c mice with TRIP/JEV vectors resulted in the production of IgGs against Japanese encephalitis virus, and the injection of a second dose one month after the prime injection greatly boosted antibody titers. The TRIP/JEV vectors elicited neutralizing antibodies against JEV strains belonging to genotypes 1, 3, and 5. Immunization of piglets with two doses of the lentiviral vector expressing JEV virus-like particles led to high titers of anti-JEV antibodies, that had efficient neutralizing activity regardless of the JEV genotype tested.
  
  
  CONCLUSIONS
  Immunization of pigs with the lentiviral vector expressing JEV virus-like particles is particularly efficient to prime antigen-specific humoral immunity and trigger neutralizing antibody responses against JEV genotypes 1, 3, and 5. The titers of neutralizing antibodies elicited by the TRIP/JEV vector are sufficient to confer protection in domestic pigs against different genotypes of JEV and this could be of a great utility in endemic regions where more than one genotype is circulating.
authors.affiliation: Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, Paris, France.
authors.forename: Mélissanne
authors.initials: M
authors.lastname: de Wispelaere
authors.affiliation: Institute of Virology and Immunology, Mittelhäusern, Switzerland.
authors.forename: Meret
authors.initials: M
authors.lastname: Ricklin
authors.affiliation: Virologie Moléculaire et Vaccinologie, Institut Pasteur, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Souque
authors.affiliation: Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, Paris, France.
authors.forename: Marie-Pascale
authors.initials: MP
authors.lastname: Frenkiel
authors.affiliation: Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Paulous
authors.affiliation: Institute of Virology and Immunology, Mittelhäusern, Switzerland.
authors.forename: Obdulio
authors.initials: O
authors.lastname: Garcìa-Nicolàs
authors.affiliation: Institute of Virology and Immunology, Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Artur
authors.initials: A
authors.lastname: Summerfield
authors.affiliation: Virologie Moléculaire et Vaccinologie, Institut Pasteur, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Charneau
authors.affiliation: Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Desprès
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D013552:Swine; D014771:Virion / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral