Production and characterization of protective human antibodies against shiga toxin 1

被引:50
作者
Mukherjee, J
Chios, K
Fishwild, D
Hudson, D
O'Donnell, S
Rich, SM
Donohue-Rolfe, A
Tzipori, S
机构
[1] Tufts Univ, Sch Vet Med, Div Infect Dis, North Grafton, MA 01536 USA
[2] Medarex, San Jose, CA USA
关键词
D O I
10.1128/IAI.70.10.5896-5899.2002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Hemolytic-uremic syndrome (HUS) is a serious complication which is predominantly associated in children with infection by Shiga toxin-producing Escherichia coli (STEC). By using HuMAb-Mouse (Medarex) animals, human monoclonal antibodies (Hu-MAbs) were developed against Shiga toxin 1 (Stx1) for passive immunotherapy of HUS. Ten stable hybridomas comprised of fully human heavy- and light-chain immunoglobulin elements and secreting Stx1-specific Hu-MAbs (seven immunoglobulin M(kappa) [IgM(kappa)] elements [one specific for the A subunit and six specific for the B subunit] and three IgG1(kappa) elements specific for subunit B) were isolated. Two IgM(kappa) Hu-MAbs (2D9 and 15G9) and three IgG1(kappa) Hu-MAbs (5A4, 10F4, and 15G2), all specific for subunit B, demonstrated marked neutralization of Stx1 in vitro and significant prolongation of survival in a murine model of Stx1 toxicosis.
引用
收藏
页码:5896 / 5899
页数:4
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