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Title: INDUCTION OF JAPANESE ENCEPHALITIS VIRUS-SPECIFIC CYTOTOXIC T LYMPHOCYTES IN HUMAN BY POXVIRUS-BASED JE VACCINE CANDIDATES

Author
item KONISHI, EIJI - KOBE UNIVERSITY, JAPAN
item KURANE, ICHIRO - UNIVERSITY OF MASS
item Mason, Peter
item SHOPE, ROBERT - YALE UNIVERSITY
item KANESA-THASAN, NIRANJAN - WALTER REED ARMY INST.,DC
item SMUCNY, JOHN - WALTER REED ARMY INST.,DC
item HOKE, CHARLES - WALTER REED ARMY INST.,DC
item ENNIS, FRANCIS - UNIVERSITY OF MASS.

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/2/1997
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. Japanese encephalitis 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 been engineered and tested genetically engineered poxviruses that encode a some of the protein immunogens 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 can be safely administered to human volunteers, and that the vaccinees produced immune responses, including antibodies and cytotoxic (killer) T- lymphocytes (cells) that are capable of destroying JEV-infected cells. However, immune responses were reduced in vaccinees who had a history of vaccination against smallpox.

Technical Abstract: Japanese encephalitis virus (JEV) is a mosquito-transmitted virus that causes disease in horses, man, and pregnant swine. The virus is an exotic pathogen, and is readily transmitted by mosquitoes found throughout the US. We have developed a genetically engineered vaccine for JEV utilizing vaccinia virus, the vaccine used to eradicate smallpox, as a live vector to carry portions of the JEV genetic information. These vaccinia virus-vectored vaccines provide protective levels of immunity in mice and swine, and are safe and immunogenic in human volunteers. However, humans with a history of vaccination against smallpox showed greatly reduced immune responses to the JEV-vaccinia vaccine candidates. To circumvent this problem, we have utilized an alternative vaccine approach, naked DNA vaccination, to stimulate immunity from JE. In this preliminary study, we have shown that naked DNA vaccines engineered to express two of the proteins of JEV, can elicit anti-JEV immunity in mace. In addition, mice given these DNA vaccines are protected from lethal challenge with JEV.