POXVIRUS-BASED JAPANESE ENCEPHALITIS VACCINE CANDIDATES INDUCE JE VIRUS-SPECIFIC CD8(-LYMPHOCYTES IN MICE() CYTOTOXIC T)

Recombinant Japanese encephalitis (JE) vaccine candidates based on a h ighly attenuated vaccinia virus (NYVAC-JEV) and a canarypox virus (ALV AC-JEV) were evaluated for their ability to induce specific antibodies and cytotoxic T lymphocytes (CTLs) in mice. Six- to eight-week-old ma le Balb/c mice that received one or two intraperitoneal inoculations w ith these JE vaccine candidates at a dose of 1 x 10(7) PFU per mouse p roduced neutralizing antibody and antibodies to the envelope (E) and n onstructural 1 (NS1) proteins as determined by radioimmunoprecipitatio n. Immunization with either of these vaccine candidates also induced J E virus-specific T lymphocytes that proliferated in response to stimul ation with infectious virus and/or noninfectious viral antigens. Mice maintained detectable levels of neutralizing antibody and JE virus-spe cific memory T cells for at least 6 months after immunization with NYV AC-JEV and for 4 months after immunization with ALVAC-JEV. Cells induc ed to proliferate after stimulation with live virus contained specific CD8(+) CTLs that lysed primary Balb/c mouse kidney cells infected wit h JE virus and P815 mastocytoma cells infected with a recombinant vacc inia virus expressing the premembrane (prM), E, and NS1 proteins. Thes e CTLs also lysed P815 cells infected with vaccinia recombinants expre ssing prM and E, and those expressing E and NS1, but did not lyse P815 cells infected with a recombinant virus expressing only NS1, indicati ng 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. (C) 199 7 Academic Press