Induction of protective immunity against Japanese encephalitis in mice by immunization with a plasmid encoding Japanese encephalitis virus premembrane and envelope genes.
A DNA vaccine plasmid containing the Japanese encephalitis (JE) virus premembrane (prM) and envelope (E) genes (designated pcDNA3JEME) was evaluated for immunogenicity and protective efficacy in mice. Two immunizations of 4-week-old female ICR mice with pcDNA3JEME by intramuscular or intradermal injections at a dose of 10 or 100 microg per mouse elicited neutralizing (NEUT) antibodies at titers of 1:10 to 1:20 (90% plaque reduction), and all immunized mice survived a challenge with 10,000 50% lethal doses of the P3 strain of JE virus. A single immunization with 100 microg of pcDNA3JEME did not elicit detectable NEUT antibodies but induced protective immunity. Spleen cells obtained from BALB/c mice immunized once with 10 or 100 microg of pcDNA3JEME contained JE virus-specific memory cytotoxic T lymphocytes (CTLs). BALB/c mice maintained detectable levels of memory B cells and CTLs for at least 6 months after one immunization with pcDNA3JEME at a dose of 100 microg. The CTLs induced in BALB/c mice immunized twice with 100 microg of pcDNA3JEME were CD8 positive and recognized mainly the envelope protein. These results indicate that pcDNA3JEME has the ability to induce a protective immune response which includes JE virus-specific antibodies and CTLs.
Konishi
E
E
Department of Medical Zoology, Kobe University School of Medicine, Kobe 650, Japan. ekon@ams.kobe-u.ac.jp
Yamaoka
M
M
Khin-Sane-Win
Kurane
I
I
Mason
P W
PW
D000818:Animals; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D015752:Genes, env; D007109:Immunity; D007114:Immunization; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*