Increased immunogenicity and protective efficacy in outbred and inbred mice by strategic carboxyl-terminal truncation of Japanese encephalitis virus envelope glycoprotein

• Published in: The American journal of tropical medicine and hygiene Vol. 48; no. 3; p. 412
• Main Authors: Jan, L R, Yang, C S, Henchal, L S, Sumiyoshi, H, Summers, P L, Dubois, D R, Lai, C J
• Format: Journal Article
• Language: English
• Published: United States 01-03-1993
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antibodies, Viral - biosynthesis; Antibodies, Viral - blood; Antigens, Viral - analysis; Base Sequence; Cell Line; DNA, Viral - chemistry; Encephalitis Virus, Japanese - genetics; Encephalitis Virus, Japanese - immunology; Encephalitis, Japanese - prevention & control; Enzyme-Linked Immunosorbent Assay; Female; Immunization; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Molecular Sequence Data; Neutralization Tests; Precipitin Tests; Radioimmunoprecipitation Assay; Sequence Alignment; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Vaccines - genetics; Viral Vaccines - immunology
• ISSN: 0002-9637
• DOI: 10.4269/ajtmh.1993.48.412

We constructed recombinant vaccinia viruses expressing the full-length envelope (E) glycoprotein of Japanese encephalitis virus (JEV) or a strategically truncated E glycoprotein, approximately 80% of the N-terminal sequence, and compared their antigenic structure and protective immunity in mice. The truncation site in the JEV E glycoprotein sequence corresponds to the position that had been shown to increase the immunogenicity of dengue type 4 or type 2 virus E glycoprotein. Analysis of the JEV E glycoprotein in recombinant virus-infected cells showed that C-terminally truncated E retains an antigenic structure similar to that of the full-length E glycoprotein. The full-length JEV E glycoprotein was detected predominantly intracellularly, while a small fraction (< 2%) was present on the cell surface. On the other hand, the truncated 80% E glycoprotein exhibited an alteration in the intracellular transport pathway resulting in increased accumulation (10-25%) on the cell surface and secretion (6-10%) into the medium. The C-terminally truncated E glycoprotein induced a greater antibody response and a higher 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 differ in their resistance to intraperitoneal (ip) JEV infection. In the case of outbred CD-1 and inbred C57/Bl 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 intracerebral JEV infection, truncated E glycoprotein induced a higher titer of JEV neutralizing antibodies.