title: Freeze-dried live attenuated smallpox vaccine prepared in cell culture "LC16-KAKETSUKEN": Post-marketing surveillance study on safety and efficacy compliant with Good Clinical Practice.
abstract: BACKGROUND
  In Japan, production of smallpox vaccine LC16m8 (named LC16-KAKETSUKEN) was restarted and was determined to be maintained as a national stockpile in March 2002.
  
  
  OBJECTIVE
  To conduct a post-marketing surveillance study of the vaccination of freeze-dried live attenuated smallpox vaccine prepared in cell culture LC16-KAKETSUKEN using attenuated vaccinia strain LC16m8. The study complied with Good Clinical Practice, focusing on a comparison between primary vaccinees and re-vaccinees.
  
  
  METHODS
  268 personnel (261 males and 7 females) of the Japan Ground Self-Defense Force were inoculated with LC16-KAKETSUKEN and thereafter adverse events and efficacy were evaluated.
  
  
  RESULTS
  Among 268 vaccinee participants, the following vaccinees showed adverse events, none serious: 53 of 196 primary vaccinees (without previous smallpox vaccination), 4 of 71 re-vaccinees (with previous smallpox vaccination) and 1 vaccinee with unknown previous vaccination history. A breakdown of adverse events observed in this study (total 268 vaccinees) showed the following minor or mild adverse events: 52 (19.4%) swelling of axillary lymph node, 4 (1.5%) fever, 2 (0.7%) fatigue, 1 (0.4%) of rash, 14 (5.2%) erythema at the inoculation site, 1 (0.4%) swelling at the inoculation site and 1 (0.4%) autoinoculation. The incidence of adverse events for primary vaccinees (53/196; 27.0%) was significantly higher than for re-vaccinees (4/71; 5.6%). However, the proportion of vaccine take was significantly higher for primary vaccinees (185/196; 94.4%) than for re-vaccinees (58/71; 81.7%). Although the proportion of vaccine take of re-vaccinees was significantly lower than for primary vaccinees due to preexisting immunity by previous vaccination, no significant difference was found in neutralizing antibody titers between primary vaccinees and re-vaccinees at 1, 4 and 7 months after LC16-KAKETSUKEN vaccination.
  
  
  CONCLUSIONS
  The present post-marketing surveillance study compliant with Good Clinical Practice demonstrated the efficacy and safety of the smallpox vaccine LC16-KAKETSUKEN in an adult population. LC16-KAKETSUKEN is the sole currently available licensed smallpox vaccine for both adult and pediatric populations.
authors.affiliation: Health Care Center, Japan Self-Defense Forces Central Hospital, 1-2-24 Ikeziri, Setagaya-ku, Tokyo 154-8532, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Nishiyama
authors.affiliation: Health Care Center, Japan Self-Defense Forces Central Hospital, 1-2-24 Ikeziri, Setagaya-ku, Tokyo 154-8532, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujii
authors.affiliation: National Institute of Public Health, 2-3-6 Minami, Wako-shi, Saitama 351-0197, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kanatani
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (Kaketsuken), 1-6-1 Okubo, Kita-ku, Kumamoto-shi, Kumamoto 860-8568, Japan. Electronic address: shinmura-ya@kaketsuken.or.jp.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Shinmura
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (Kaketsuken), 1-6-1 Okubo, Kita-ku, Kumamoto-shi, Kumamoto 860-8568, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yokote
authors.affiliation: Chiba University, 1-33, Yayoicho, Inage Ward, Chiba-shi, Chiba 263-8522, Japan.
authors.forename: So
authors.initials: S
authors.lastname: Hashizume
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D018929:Cell Culture Techniques; D005260:Female; D005612:Freeze Drying; D006801:Humans; D017589:Immunization Programs; D007117:Immunization, Secondary; D007564:Japan; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D012899:Smallpox / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology* / Q000592:standards; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated; C539069:smallpox vaccine LC16m8
keywords: Attenuated smallpox vaccine; Efficacy; LC16-KAKETSUKEN; LC16m8; Postmarketing surveillance study; Safety