title: A poorly neutralizing IgG2a/c response elicited by a DNA vaccine protects mice against Japanese encephalitis virus.
abstract: We demonstrated previously that immunization with a DNA vaccine expressing the Japanese encephalitis virus (JEV) envelope (E) protein conferred a high level of protection through a poorly neutralizing antibody response. Here, we further investigated the role of the IgG subclass in this antibody-dependent protection using cytokine co-immunization and cytokine-deficient mice. A significant difference in IgG2a/c but not IgG1 was observed between mice that survived or died following a lethal challenge. Correspondingly, the IgG2a/c response and protection increased in IL-4-deficient mice but decreased in IFN-γ-deficient mice, highlighting the importance of IgG2a/c. In addition, the restoration of protection and E-specific IgG2a/c production in IFN-γ-deficient mice by a T helper (Th) type 1-biased intramuscular immunization suggested that IgG2a/c but not IFN-γ was the major component for protection. The failure of protection against a direct intracranial challenge indicated that IgG2a/c-mediated protection was restricted to outside the central nervous system. Consistent with this conclusion, passive transfer of E-specific antisera conferred protection only pre-exposure to JEV. Therefore, our data provided evidence that the IgG subclass plays an important role in protection against JEV, particular in poorly neutralizing E-specific antibodies, and Th1-biased IgG2a/c confers better protection than Th2-biased IgG1 against JEV.
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.|National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Hsin-Wei
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Institutes of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Huang
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Hui-Mei
authors.initials: HM
authors.lastname: Hu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Han-Hsuan
authors.initials: HH
authors.lastname: Chung
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Szu-Hsien
authors.initials: SH
authors.lastname: Wu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.affiliation: Institutes of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Mi-Hua
authors.initials: MH
authors.lastname: Tao
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.|National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Chien-Hsiung
authors.initials: CH
authors.lastname: Pan
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology / Q000821:virology; D004664:Encephalitis Virus, Japanese / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D005260:Female; D007114:Immunization; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007074:Immunoglobulin G / Q000145:classification* / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D022321:Japanese Encephalitis Vaccines / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D022321:Japanese Encephalitis Vaccines; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D015847:Interleukin-4; D007371:Interferon-gamma