Protective immunity of E. coli-synthesized NS1 protein of Japanese encephalitis virus.
Immunogenicity and protective efficacy of recombinant Japanese encephalitis virus (JEV) NS1 proteins generated using DNA vaccines and recombinant viruses have been demonstrated to induce protection in mice against a challenge of JEV at a lethal dose. The West Nile virus NS1 region expressed in E. coli is recognized by these protective monoclonal antibodies and, in this study, we compare immunogenicity and protective immunity of the E. coli-synthesized NS1 protein with another protective immunogen, the envelope domain III (ED3). Pre-challenge, detectable titers of JEV-specific neutralizing antibody were detected in the immunized mice with E. coli-synthesized ED3 protein (PRNT50 = 1:28) and the attenuated JEV strain T1P1 (PRNT50 = 1:53), but neutralizing antibodies were undetectable in the immunized mice with E. coli-synthesized NS1 protein (PRNT50 < 1:10). However, the survival rate of the NS1-immunized mice against the JEV challenge was 87.5% (7/8), showing significantly higher levels of protection than the ED3-immunized mice, 62.5% (5/8) (P = 0.041). In addition, E. coli-synthesized NS1 protein induced a significant increase of anti-NS1 IgG1 antibodies, resulting in an ELISA titer of 100,1000 in the immunized sera before lethal JEV challenge. Surviving mice challenged with the virulent JEV strain Beijing-1 showed a ten-fold or greater rise in IgG1 and IgG2b titers of anti-NS1 antibodies, implying that the Th2 cell activation might be predominantly responsible for antibody responses and mice protection.
Lin
Cheng-Wen
CW
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan, ROC. cwlin@mail.cmu.edu.tw
Liu
Kuang-Ting
KT
Huang
Hong-Da
HD
Chen
Wei-June
WJ
D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D004664:Encephalitis Virus, Japanese / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
C100315:NS1 protein, Flavivirus; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins