Poxvirus-based Japanese encephalitis vaccine candidates induce JE virus-specific CD8+ cytotoxic T lymphocytes in mice.
Recombinant Japanese encephalitis (JE) vaccine candidates based on a highly attenuated vaccinia virus (NYVAC-JEV) and a canarypox virus (ALVAC-JEV) were evaluated for their ability to induce specific antibodies and cytotoxic T lymphocytes (CTLs) in mice. Six- to eight-week-old male Balb/c mice that received one or two intraperitoneal inoculations with these JE vaccine candidates at a dose of 1 x 10(7) PFU per mouse produced neutralizing antibody and antibodies to the envelope (E) and nonstructural 1 (NS1) proteins as determined by radioimmunoprecipitation. Immunization with either of these vaccine candidates also induced JE virus-specific T lymphocytes that proliferated in response to stimulation with infectious virus and/or noninfectious viral antigens. Mice maintained detectable levels of neutralizing antibody and JE virus-specific memory T cells for at least 6 months after immunization with NYVAC-JEV and for 4 months after immunization with ALVAC-JEV. Cells induced to proliferate after stimulation with live virus contained specific CD8+ CTLs that lysed primary Balb/c mouse kidney cells infected with JE virus and P815 mastocytoma cells infected with a recombinant vaccinia virus expressing the premembrane (prM), E, and NS1 proteins. These CTLs also lysed P815 cells infected with vaccinia recombinants expressing prM and E, and those expressing E and NS1, but did not lyse P815 cells infected with a recombinant virus expressing only NS1, indicating that the CTLs mainly recognized E, but did not recognize NS1. These results demonstrate that both recombinant JE vaccines, NYVAC-JEV and ALVAC-JEV, induce JE virus-specific antibody and CTLs in mice.
Konishi
E
E
Department of Medical Zoology, Kobe University School of Medicine, Chuo-ku, Japan. ekon@icluna.kobe-u.ac.jp
Kurane
I
I
Mason
P W
PW
Shope
R E
RE
Ennis
F A
FA
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000917:Antibody Formation; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004672:Encephalitis, Japanese / Q000276:immunology*; D005416:Flavivirus / Q000276:immunology*; D007668:Kidney; D008212:Lymphocyte Depletion; D008297:Male; D012515:Mast-Cell Sarcoma; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011212:Poxviridae; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology*; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014616:Vaccinia virus; D014764:Viral Proteins / Q000276:immunology*; D014765:Viral Vaccines
D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines