Novel neutralizing human monoclonal antibodies against tetanus neurotoxin.

Autor: Minamitani T; Laboratory of Infectious Diseases and Immunity, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki City, Osaka, 567-0085, Japan.; Laboratory of Immunobiologics Evaluation, Center for Vaccine and Adjuvant Research (CVAR), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki City, Osaka, 567-0085, Japan., Kiyose K; Laboratory of Infectious Diseases and Immunity, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki City, Osaka, 567-0085, Japan.; Laboratory of Immunobiologics Evaluation, Center for Vaccine and Adjuvant Research (CVAR), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki City, Osaka, 567-0085, Japan., Otsubo R; Laboratory of Pharmaceutical Integrated Omics, Department of Pharmaceutical Engineering, Facility of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan., Ito T; Laboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki City, Osaka, 567-0085, Japan., Akiba H; Laboratory of Advanced Biopharmaceuticals, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki City, Osaka, 567-0085, Japan., Furuta RA; Japanese Red Cross Central Blood Institute, 1-67 Tatsumi, Koto-ku, Tokyo, 135-8521, Japan., Inoue T; Division of Advance Pharmaco-Science, Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamada-oka, Suita, Osaka, 565-0871, Japan., Tsumoto K; Center for Drug Discovery Research (CDDR), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki City, Osaka, 567-0085, Japan.; Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.; Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8656, Japan., Satake M; Japanese Red Cross Central Blood Institute, 1-67 Tatsumi, Koto-ku, Tokyo, 135-8521, Japan., Yasui T; Laboratory of Infectious Diseases and Immunity, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki City, Osaka, 567-0085, Japan. tyasui@nibiohn.go.jp.; Laboratory of Immunobiologics Evaluation, Center for Vaccine and Adjuvant Research (CVAR), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki City, Osaka, 567-0085, Japan. tyasui@nibiohn.go.jp.; Laboratory of Pharmaceutical Integrated Omics, Department of Pharmaceutical Engineering, Facility of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan. tyasui@nibiohn.go.jp.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Jun 09; Vol. 11 (1), pp. 12134. Date of Electronic Publication: 2021 Jun 09.
DOI: 10.1038/s41598-021-91597-2
Abstrakt: Tetanus is a fatal disease caused by tetanus neurotoxin (TeNT). TeNT is composed of a light chain (Lc) and a heavy chain, the latter of which is classified into two domains, N-terminus Hn and C-terminus Hc. Several TeNT-neutralizing antibodies have been reported, but it remains unclear which TeNT domains are involved in neutralization. To further understand the mechanism of these antibodies, we isolated TeNT-reactive human antibody clones from peripheral blood mononuclear cells. We then analyzed the reactivity of the isolated antibody clones to each protein domain and their inhibition of Hc-ganglioside GT1b binding, which is critical for TeNT toxicity. We also investigated the TeNT-neutralizing ability of isolated antibody clones and showed that an Hn-reactive clone protected strongly against TeNT toxicity in mice. Furthermore, combination treatment of Hn-reactive antibody clones with both Hc-reactive and TeNT mix (the mixture of Hc, Hn, and Lc proteins)-reactive antibody clones enhanced the neutralizing effect. These results indicated that antibody clones targeting Hn effectively neutralized TeNT. In addition, the use of a cocktail composed of Hc-, Hn-, and TeNT mix-reactive antibodies provided enhanced protection compared to the use of each antibody alone.
Databáze: MEDLINE