A Lentiviral Vector Expressing Japanese Encephalitis Virus-like Particles Elicits Broad Neutralizing Antibody Response in Pigs

PLoS Negl Trop Dis. 2015 Oct 5;9(10):e0004081. doi: 10.1371/journal.pntd.0004081. eCollection 2015.

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.

Methodology/principal findings: 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/significance: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood*
  • Encephalitis Virus, Japanese / genetics
  • Encephalitis Virus, Japanese / immunology*
  • Female
  • Genetic Vectors
  • HEK293 Cells
  • Humans
  • Lentivirus / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Swine
  • Virion / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral

Grant support

The research leading to these results and MdW, MR received funding from the European Union’s Seventh Framework Program for research, technological development and demonstration under Grant Agreement no 278433-PREDEMICS. website: http://predemics.biomedtrain.eu, European Commission CORDIS: http://cordis.europa.eu/result/rcn/55956_en.html. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.