title: Comparison of the immunogenicity of botulinum toxin type A and the efficacy of A1 and A2 neurotoxins in animals with A1 toxin antibodies.
abstract: One issue with botulinum toxin type A products is a reduced therapeutic response in patients that have been injected with frequent dosing over a prolonged period. A possible cause of this is hemagglutinin, found in progenitor toxins, displaying adjuvant activity, enhancing antibody production against the toxin. We investigated whether there is any difference in immunogenicity between the LL toxin-derived subtype A1 (A1LL) and the neurotoxin-derived subtypes A1 and A2 (A1NTX and A2NTX, respectively), and investigated whether A2NTX is effective in animals which produce antibodies against A1LL. Neutralizing antibodies were detected in the A1LL-administered group; however, they were not detected in swine and rabbits administered multiple doses of A2NTX. These results indicate that A2NTX has a lower immunogenicity than A1LL. In rats with neutralizing antibodies, produced by the administration of A1LL, that were administered either A1NTX or A2NTX, A2NTX showed more potent inhibitory neuromuscular transmission than A1NTX. In human sera immunized with the botulinum toxoid vaccine (containing LL, L, and M toxoid derived subtype A1) reacted with either A1NTX or A2NTX, A2NTX showed more potent inhibitory neuromuscular transmission than A1NTX. This suggests that A2NTX has a greater therapeutic value in humans who have neutralizing antibodies against the A1 toxin.
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1-6-1 Okubo, Kita-ku, Kumamoto-shi, Kumamoto 860-8568, Japan; Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan. Electronic address: chabo@pop17.odn.ne.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Torii
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1-6-1 Okubo, Kita-ku, Kumamoto-shi, Kumamoto 860-8568, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Goto
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1-6-1 Okubo, Kita-ku, Kumamoto-shi, Kumamoto 860-8568, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakahira
authors.affiliation: Department of Veterinary Sciences, School of Life and Environmental Sciences, Osaka Prefecture University, 1-18 Rinku-oraikita, Izumisano-shi, Osaka 598-8531, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Kozaki
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1-6-1 Okubo, Kita-ku, Kumamoto-shi, Kumamoto 860-8568, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ginnaga
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D019274:Botulinum Toxins, Type A / Q000032:analysis / Q000276:immunology* / Q000633:toxicity*; D003014:Clostridium botulinum / Q000737:chemistry* / Q000145:classification; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009500:Neutralization Tests; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013552:Swine; D018675:Toxicity Tests
chemical_list: D057134:Antibodies, Neutralizing; D019274:Botulinum Toxins, Type A
keywords: Antibody; Botulinum toxin; ELISA; Immunogenicity; Neutralization; Rat CMAP neutralization test