title: Comparative human and mouse antibody responses against tetanus toxin at clonal level.
abstract: Tetanus is a highly fatal disease caused by tetanus neurotoxin (TeNT) and remains a major threat to human and animal health, despite preventive strategies. TeNT is composed of heavy and light chain linked by a disulfide bond. The antibody response to TeNT is polyclonal and directed to multiple epitopes within both the light and heavy chains, leading to toxin neutralization. This study was undertaken to localize and compare neutralizing epitopes recognized by human and mouse TeNT-specific antibodies at a clonal level. In the present study, 22 murine hybridoma clones and 50 human lymphoblastoid cell lines secreting monoclonal antibodies (mAb) were generated against TeNT. The specificity of these mAb was determined using different recombinant fragments of tetanus toxin. Moreover, this study investigated the in vitro toxin neutralizing activity of these mAb by a ganglioside GT1b assay. The results showed that tetanus toxoid immunization in humans and BALB/c mice induced a vigorous humoral immune response against different fragments of TeNT, particularly the carboxyl-terminal fragment of the heavy chain (known as fragment C). The fragment C-specific human and mouse mAb could largely neutralize TeNT. However, while all fragment C-specific human mAb reacted with the carboxyl-terminal part of this fragment (H(CC)), the majority of the mouse mAb failed to recognize this region. These results suggested that fragment C is the major target for the TeNT neutralizing antibodies, although different epitopes seem to be targeted by human and mouse antibodies.
authors.affiliation: a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .|b Department of Immunology , School of Medicine, Tabriz University of Medical Sciences , Tabriz , Iran .
authors.forename: Mehdi
authors.initials: M
authors.lastname: Yousefi
authors.affiliation: a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Vahid
authors.initials: V
authors.lastname: Younesi
authors.affiliation: c Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR , Tehran , and.
authors.forename: Ali Ahmad
authors.initials: AA
authors.lastname: Bayat
authors.affiliation: a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Farhad
authors.initials: F
authors.lastname: Jadidi-Niaragh
authors.affiliation: d Department of Bacterial Vaccines , Razi Vaccine and Serum Research Institute , Karaj , Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Abbasi
authors.affiliation: a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Alireza
authors.initials: A
authors.lastname: Razavi
authors.affiliation: a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Roya
authors.initials: R
authors.lastname: Khosravi-Eghbal
authors.affiliation: a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Hossein
authors.initials: H
authors.lastname: Asgarian-Omran
authors.affiliation: a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .|c Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR , Tehran , and.
authors.forename: Fazel
authors.initials: F
authors.lastname: Shokri
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D013045:Species Specificity; D013744:Tetanus Toxin / Q000494:pharmacology*
chemical_list: D000907:Antibodies, Bacterial; D058846:Antibodies, Monoclonal, Murine-Derived; D057134:Antibodies, Neutralizing; D013744:Tetanus Toxin
keywords: Fragment C; TeNT; immune response; neutralizing antibodies