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Title: POXVIRUS-BASED JAPANESE ENCEPHALITIS VACCINE CANDIDATES INDUCE JE VIRUS- SPECIFIC CD8+ CYTOTOXIC T LYMPHOCYTES IN MICE

Author
item KONISHI, EIJI - KOBE UNIVERSITY, JAPAN
item KURANE, ICHIRO - U OF MA, WORCESTER, MASS
item Mason, Peter
item SHOPE, ROBERT - YALE UNIV., NEW HAVEN, CT
item ENNIS, FRANCIS - U OF MA, WORCESTER, MASS

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/4/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: Japanese encephalitis (JE) is a mosquito-borne viral disease that infects pigs, horses, and humans in many areas of the Far East and Southeast Asia. JE virus (JEV) infection of pregnant swine can cause abortion, and many of the successfully delivered offspring suffer irreversible brain damage. JEV infections of humans or horses can result in a severe brain infection known as encephalitis. Current vaccines for JE consist of chemically inactivated viruses prepared from JEV-infected suckling mice. Preparation of these vaccines is dangerous and time consuming. In an attempt to develop new vaccines, we have engineered and tested genetically engineered poxviruses that encode some of the proteins of JEV. These poxviruses have been shown to be safe and effective vaccines for JE in mice and swine. The current work describes the further characterization of these recombinant poxviruses. Specifically, we have demonstrated that these viruses induce mice to produce cytotoxic (killer) T-lymphocytes (cells) that are capable of destroying JEV-infected cells. These T-cells are also present in animals infected with JEV, and their induction by the poxviruses demonstrates that these recombinant-derived vaccines are effective in inducing killer T-cells, and important indicator of their effectiveness in animals.

Technical Abstract: Recombinant 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 8-wk-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 non-structural 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 non-infectious 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 a 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.