Non-clinical and phase I clinical trials of a Vero cell-derived inactivated Japanese encephalitis vaccine.
The safety and effectiveness of a Vero cell-derived inactivated Japanese encephalitis (JE) vaccine were compared with those of a current JE vaccine in non-clinical studies and a phase I clinical trial. The single-dose toxicity study showed no toxicity of either the current JE vaccine or the investigational Vero cell-derived JE vaccine. In a local irritation study, the degree of irritation caused by both vaccines was determined to be the same as that induced by normal saline. To investigate genotoxicity, a chromosomal aberration test was conducted and the results were negative. Both JE vaccines were administered to a group of 30 subjects who were seronegative (neutralizing antibody titer <10(1)) for JEV virus (Beijing-1 Strain). Each subject was subcutaneously inoculated twice at an interval of 1-4 weeks, followed by an additional booster inoculation 4-8 weeks later, and clinical reactions and serological responses were subsequently investigated. Adverse drug reactions of local reaction, headache and malaise were mild, occurring at a rate of 6.7 and 20.0% after administration of the Vero cell-derived JE vaccine and the current JE vaccine, respectively. The seroconversion rate after three doses of both JE vaccines was 100%, while the geometric mean titer for the Vero cell-derived and current JE vaccines was 10(2.35) and 10(2.03), respectively. These results suggest that the safety and effectiveness of the Vero cell-derived inactivated JE vaccine are equal to those of the currently available conventional vaccine in humans, and that the Vero cell-derived vaccine could be a useful second-generation JE vaccine.
The Chemo-Sero-Therapeutic Research Institute, Kikuchi Research Center, Kawabe Kyokushi, Kikuchi, Kumamoto 869-1298, Japan. kuzuhara@kaketsuken.or.jp
Syoji
S
Kuzuhara
Hideki
H
Nakamura
Kenshi
K
Hayashida
Junko
J
Obata
Motoharu
M
Abe
Kengo
K
Sonoda
Kiyoto
K
Nishiyama
Keishin
K
Sugawara
Kengo
K
Takeda
Tomitaka
T
Honda
Hajime
H
Matsui
Takamichi
T
Shigaki
Yoichiro
Y
Kino
Hiroshi
H
Mizokami
Masahiko
M
Tanaka
Kyosuke
K
Mizuno
Kohji
K
Ueda
D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002869:Chromosome Aberrations / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D006801:Humans; D007115:Immunization Schedule; D007509:Irritants; D022321:Japanese Encephalitis Vaccines / Q000009:adverse effects / Q000627:therapeutic use* / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011786:Quality Control; D011817:Rabbits; D015164:Vaccines, Inactivated / Q000627:therapeutic use; D014709:Vero Cells
D000914:Antibodies, Viral; D007509:Irritants; D022321:Japanese Encephalitis Vaccines; D015164:Vaccines, Inactivated