INCREASED IMMUNOGENICITY AND PROTECTIVE EFFICACY IN OUTBRED AND INBRED MICE BY STRATEGIC CARBOXYL-TERMINAL TRUNCATION OF JAPANESE ENCEPHALITIS-VIRUS ENVELOPE GLYCOPROTEIN

We constructed recombinant vaccinia viruses expressing the full-length envelope (E) glycoprotein of Japanese encephalitis virus (JEV) or a s trategically truncated E glycoprotein, approximately 80% of the N-term inal sequence, and compared their antigenic structure and protective i mmunity in mice. The truncation site in the JEV E glycoprotein sequenc e corresponds to the position that had been shown to increase the immu nogenicity of dengue type 4 or type 2 virus E glycoprotein. Analysis o f the JEV E glycoprotein in recombinant virus-infected cells showed th at C-terminally truncated E retains an antigenic structure similar to that of the full-length E glycoprotein. The full-length JEV E glycopro tein was detected predominantly intracellularly, while a small fractio n (< 2%) was present on the cell surface. On the other hand, the trunc ated 80% E glycoprotein exhibited an alteration in the intracellular t ransport pathway resulting in increased accumulation (10-25%) on the c ell surface and secretion (6-10%) into the medium. The C-terminally tr uncated E glycoprotein induced a greater antibody response and a highe r level of protective immunity than did the full-length E glycoprotein in outbred CD-1 mice as well as in two strains of inbred mice that di ffer in their resistance to intraperitoneal (ip) JEV infection. In the case of outbred CD-1 and inbred C57/B1 mice, which possess a dominant autosomal genetic locus that controls resistance to a high dose of ip infection of JEV or the capacity to acquire resistance to intracerebr al JEV infection, truncated E glycoprotein induced a higher titer of J EV neutralizing antibodies.