title: Clinical Study of New Tetravalent (Type A, B, E, and F) Botulinum Toxoid Vaccine Derived from M Toxin in Japan.
abstract: Botulinum toxin is the most poisonous substance known, and is believed to be a highly lethal as a biological weapon; researchers of the toxin are exposed to this hazard. Botulinum toxoid vaccines have been produced and used in Japan. However, since clinical studies involving these vaccines were conducted before establishment of the Ethical Guidelines for Clinical Research in Japan, their immunogenicity and safety were not systematically assessed. In this study, we produced a new tetravalent (type A, B, E, and F) botulinum toxoid vaccine, the first ever to be derived from M toxin, and conducted quality control tests with reference to the Minimum Requirements in Japan for adsorbed tetanus toxoid vaccine. Subsequently, a clinical study using the new vaccine in 48 healthy adult volunteers was conducted according to the guidelines in Japan. No clinically serious adverse event was noted. Neutralizing antibody titers for each type of toxin in the participants' sera, 1 month after the 4th injection were more than 0.25 IU/mL, indicating sufficient protection. This study demonstrated that the vaccine has marked immunogenicity and is safe for use in humans.
authors.affiliation: Department of Animal Science, Tokyo University of Agriculture.|Graduate School of Medicine, Osaka University.|The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN).
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Torii
authors.affiliation: Graduate School of Medicine, Osaka University.
authors.forename: Nakaba
authors.initials: N
authors.lastname: Sugimoto
authors.affiliation: Department of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kohda
authors.affiliation: Department of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University.
authors.forename: Shunji
authors.initials: S
authors.lastname: Kozaki
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN).
authors.forename: Kazunori
authors.initials: K
authors.lastname: Morokuma
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN).
authors.forename: Yoshikane
authors.initials: Y
authors.lastname: Horikawa
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN).
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ginnaga
authors.affiliation: National Institute of Infectious Diseases.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: Pharmaceuticals and Medical Devices Agency.
authors.forename: Motohide
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000818:Animals; D000992:Antitoxins / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000302:isolation & purification; D001905:Botulinum Toxins / Q000276:immunology*; D001906:Botulism / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D064368:Healthy Volunteers; D006801:Humans; D007564:Japan; D008297:Male; D051379:Mice; D008875:Middle Aged; D014121:Toxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000302:isolation & purification; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000992:Antitoxins; D001428:Bacterial Vaccines; D014121:Toxoids; D001905:Botulinum Toxins
keywords: botulinum toxoid vaccine; clinical study; neutralizing antibody; quality control tests