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

• Published in: Virology journal 2012-07, Vol.9 (1), p.135-135, Article 135
• Main Authors: Li, Yize, Counor, Dorian, Lu, Peng, Duong, Veasna, Yu, Yongxin, Deubel, Vincent
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Analysis; Animals; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antigens; Antiviral agents; Cell Line; Disease Models, Animal; Drosophila; Encephalitis Virus, Japanese - immunology; Encephalitis, Japanese - immunology; Encephalitis, Japanese - prevention & control; Female; Genetic aspects; Health aspects; Immune response; Immunization, Passive; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; Interferon gamma; Interferon-gamma - secretion; Japanese encephalitis; Japanese Encephalitis Vaccines - administration & dosage; Japanese Encephalitis Vaccines - immunology; Japanese encephalitis virus; Leukocytes, Mononuclear - immunology; Medical research; Medicine, Experimental; Mice; Mice, Inbred C3H; Monoclonal antibodies; Mosquitoes; Mouse model; NS1 protein; Proteins; Spleen - immunology; T cells; T-cell response, Antibodies; Vaccination; Vaccines; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; Viral Nonstructural Proteins - immunology; Viral proteins; Virus diseases; Viruses
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/1743-422X-9-135

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. 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. 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.