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

• Main Authors: Li Yize, Counor Dorian, Lu Peng, Duong Veasna, Yu Yongxin, Deubel Vincent
• Format: Article
• Language: English
• Published: BMC 2012-07-01
• Series: Virology Journal
• Subjects: Japanese encephalitis virus; T-cell response, Antibodies; Monoclonal antibodies; NS1 protein; Mouse model
• Online Access: http://www.virologyj.com/content/9/1/135

<p>Abstract</p> <p>Background</p> <p>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 <it>E. coli</it>-expressed JEV NS1 to immunize mice induced protection against lethal challenge; however, the protection mechanism through cellular and humoral immune responses was not described.</p> <p>Results</p> <p>JEV NS1 was expressed in and purified from <it>Drosophila</it> 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.</p> <p>Conclusion</p> <p>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 anti-viral immunity</p>