TY - JOUR
T1 - Single chain variable fragment antibodies against shiga toxins isolated from a human antibody phage display library
AU - Neri, Paola
AU - Shigemori, Naoko
AU - Hamada-Tsutsumi, Susumu
AU - Tsukamoto, Kentaro
AU - Arimitsu, Hideyuki
AU - Shimizu, Toshiyasu
AU - Akahori, Yasushi
AU - Kurosawa, Yoshikazu
AU - Tsuji, Takao
N1 - Funding Information:
This work was supported in part by a grant-in-aid for the 21st Century Center of Excellence Program of Fujita Health University from the Ministry of Education, Culture, Sports, Science, and Technology (to Y.K.).
PY - 2011/7/26
Y1 - 2011/7/26
N2 - Shiga toxins (Stxs) are involved in the pathogenesis of hemolytic-uremic syndrome and other severe systemic complications following enterohemorrhagic Escherichia coli infection in humans. Passive immunotherapies using monoclonal antibodies have been shown to be effective for neutralizing the toxic effects of Stxs. However, animal-derived monoclonal antibodies are sometimes immunogenic and their production is both laborious and expensive. We here report the isolation of single-chain variable fragment antibodies against Stxs by screening a phage display library constructed from a naïve human repertoire. An antibody among the selected clones designated B22 bound to the binding subunits of both Stx-1 and Stx-2, and strongly neutralized the cytotoxicity of Stx-1. This is the first example of a monovalent antibody showing Stx-neutralizing activity. The B22 antibody is also completely naturally occurring in human, which reduces the possibility of adverse immunological effects, and can be easily produced using bacterial protein synthesis systems.
AB - Shiga toxins (Stxs) are involved in the pathogenesis of hemolytic-uremic syndrome and other severe systemic complications following enterohemorrhagic Escherichia coli infection in humans. Passive immunotherapies using monoclonal antibodies have been shown to be effective for neutralizing the toxic effects of Stxs. However, animal-derived monoclonal antibodies are sometimes immunogenic and their production is both laborious and expensive. We here report the isolation of single-chain variable fragment antibodies against Stxs by screening a phage display library constructed from a naïve human repertoire. An antibody among the selected clones designated B22 bound to the binding subunits of both Stx-1 and Stx-2, and strongly neutralized the cytotoxicity of Stx-1. This is the first example of a monovalent antibody showing Stx-neutralizing activity. The B22 antibody is also completely naturally occurring in human, which reduces the possibility of adverse immunological effects, and can be easily produced using bacterial protein synthesis systems.
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U2 - 10.1016/j.vaccine.2011.05.093
DO - 10.1016/j.vaccine.2011.05.093
M3 - Article
C2 - 21664401
AN - SCOPUS:79960380767
SN - 0264-410X
VL - 29
SP - 5340
EP - 5346
JO - Vaccine
JF - Vaccine
IS - 33
ER -