Non-clinical and phase I clinical trials of a Vero cell-derived inactivated Japanese encephalitis vaccine

• Published in: Vaccine Vol. 21; no. 31; pp. 4519 - 4526
• Main Authors: Kuzuhara, Syoji, Nakamura, Hideki, Hayashida, Kenshi, Obata, Junko, Abe, Motoharu, Sonoda, Kengo, Nishiyama, Kiyoto, Sugawara, Keishin, Takeda, Kengo, Honda, Tomitaka, Matsui, Hajime, Shigaki, Takamichi, Kino, Yoichiro, Mizokami, Hiroshi, Tanaka, Masahiko, Mizuno, Kyosuke, Ueda, Kohji
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 07.11.2003; Elsevier; Elsevier Limited
• Subjects: Adult; Animals; Antibodies, Viral - analysis; Antigens; Arboviral encephalitis; Arboviroses; Biological and medical sciences; Brain; Cells, Cultured; Cercopithecus aethiops; Chromosome aberrations; Chromosome Aberrations - drug effects; Clinical study; Cricetinae; Cricetulus; Dogs; Fundamental and applied biological sciences. Psychology; Genotoxicity; Headaches; Human viral diseases; Humans; Immunization; Immunization Schedule; Infectious diseases; Irritants; Japanese encephalitis; Japanese Encephalitis Vaccines - adverse effects; Japanese Encephalitis Vaccines - therapeutic use; Japanese Encephalitis Vaccines - toxicity; Japanese encephalitis virus; Male; Medical sciences; Mice; Mice, Inbred ICR; Microbiology; Quality Control; Rabbits; Rodents; Side effects; Studies; Tropical viral diseases; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Inactivated - therapeutic use; Vector-borne diseases; Ventilation; Vero cell; Vero Cells; Viral diseases; Virology; Japan; Vaccine; Vero cell; Japanese encephalitis; Clinical study; Infection; Viral disease; Arbovirus disease; Central nervous system disease; Phase I trial; Cerebral disorder
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(03)00506-1

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.