We previously demonstrated that immunization with a DNA vaccine expressing the JEV envelope (E) protein conferred a high level of protection through a poorly neutralizing antibody response. In this report, we further investigated the role of 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-gamma-deficient mice, highlights the importance of IgG2a/c. In addition, the restoration of protection and E-specific IgG2a/c production in IFN-gamma-deficient mice by a Th1-biased intramuscular immunization suggests that IgG2a/c but not IFN-gamma is the major component for protection. The failure of protection against a direct intracranial challenge indicated that IgG2a/c-mediated protection is restricted to outside the CNS. Consistent with this conclusion, passive transfer of E-specific antisera conferred protection only pre-exposure to JEV. Therefore, our data here provide evidence that IgG subclass plays an important role in the protection against JEV, particular in poorly neutralizing E-specific antibodies; and Th1-biased IgG2a/c confers a better protection than Th2-biased IgG1 to against JEV.
Date:
2014-09
Relation:
Journal of General Virology. 2014 Sep;95(Pt 9):1983-1990.
