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 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.
Jan
L R
LR
Molecular Viral Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Yang
C S
CS
Henchal
L S
LS
Sumiyoshi
H
H
Summers
P L
PL
Dubois
D R
DR
Lai
C J
CJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D000956:Antigens, Viral / Q000032:analysis; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000737:chemistry; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011233:Precipitin Tests; D015531:Radioimmunoprecipitation Assay; D016415:Sequence Alignment; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral; D008562:Membrane Glycoproteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C080628:glycoprotein E, Japanese encephalitis virus