Protective immunity to Japanese encephalitis virus associated with anti-NS1 antibodies in a mouse model

Yize Li, Dorian Counor, Peng Lu, Veasna Duong, Yongxin Yu, Vincent Deubel

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background: Japanese encephalitis virus (JEV) is a major mosquito-borne pathogen that causes viral encephalitis throughout Asia. Vaccination with an inactive JEV particle or attenuated virus is an efficient preventative measure for controlling infection. Flavivirus NS1 protein is a glycoprotein secreted during viral replication that plays multiple roles in the viral life cycle and pathogenesis. Utilizing JEV NS1 as an antigen in viral vectors induces a limited protective immune response against infection. Previous studies using E. coli-expressed JEV NS1 to immunize mice induced protection against lethal challenge; however, the protection mechanism through cellular and humoral immune responses was not described. Results: JEV NS1 was expressed in and purified from Drosophila S2 cells in a native glycosylated multimeric form, which induced T-cell and antibody responses in immunized C3H/HeN mice. Mice vaccinated with 1 μg NS1 with or without water-in-oil adjuvant were partially protected against viral challenge and higher protection was observed in mice with higher antibody titers. IgG1 was preferentially elicited by an adjuvanted NS1 protein, whereas a larger load of IFN-γ was produced in splenocytes from mice immunized with aqueous NS1. Mice that passively received anti-NS1 mouse polyclonal immune sera were protected, and this phenomenon was dose-dependent, whereas protection was low or delayed after the passive transfer of anti-NS1 MAbs. Conclusion: The purified NS1 subunit induced protective immunity in relation with anti-NS1 IgG1 antibodies. NS1 protein efficiently stimulated Th1-cell proliferation and IFN-γ production. Protection against lethal challenge was elicited by passive transfer of anti-NS1 antisera, suggesting that anti-NS1 antibodies play a substantial role in antiviral immunity.

Original languageEnglish (US)
Article number135
JournalVirology Journal
Volume9
DOIs
StatePublished - 2012
Externally publishedYes

Keywords

  • Japanese encephalitis virus
  • Monoclonal antibodies
  • Mouse model
  • NS1 protein
  • T-cell response, Antibodies

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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