An organophosphorus hapten used in the preparation of monoclonal antibody and as an active immunization vaccine in the detoxication of soman poisoning.
Soman is an organophosphorus neurotoxin which inhibits the activity of acetylcholinesterase (AChE). The goal of this work was to find out whether antibodies against an organophosphorus hapten could protect mice from soman toxicity. An organophosphorus hapten P6 was synthesized. Its chemical conjugates with limulus polyphemus hemocyanin and bovine serum albumin were used as immune antigen (P6-LPH) and detection antigen (P6-BSA), respectively. Eight hybridoma cell lines secreting monoclonal antibodies (Mabs) were established. The binding reactivities of Mabs with P6 and soman were determined by competitive inhibition enzyme immunoassay (CIEIA). All antibodies recognized P6 and four of them (2C10, 3G1, 3B9 and 3C11) combined with soman. The IC(50) was 10(-6.5) to 10(-5.3)mol/l for P6 and 10(-5) to 10(-3.5)mol/l for soman. Furthermore, Mab 3G1 reduced the inhibition of AChE activity by soman in vitro. When soman was pre-incubated with Mabs before being injected into mice, soman potency was reduced, indicating that Mabs could protect mice from soman toxicity. In an active immunization regimen, mice immunized with P6-LPH and challenged with 0.15mg/kg soman injected subcutaneously, had fewer signs of intoxication and a higher survival rate compared with control mice. These results demonstrate that the anti-soman antibodies have proper characteristics as scavengers in the detoxication of soman poisoning.
Jia
Peiyuan
P
Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, China.
Wang
Yuxia
Y
Yu
Ming
M
Wu
Junhua
J
Yang
Rifang
R
Zhao
Yu
Y
Zhou
Lijun
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000918:Antibody Specificity; D002417:Cattle; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D005260:Female; D006241:Haptens / Q000276:immunology*; D006433:Hemocyanins / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009943:Organophosphorus Compounds / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000276:immunology; D012999:Soman / Q000633:toxicity*; D014611:Vaccination; D014612:Vaccines
D000911:Antibodies, Monoclonal; D002800:Cholinesterase Inhibitors; D006241:Haptens; D009943:Organophosphorus Compounds; D014612:Vaccines; D012710:Serum Albumin, Bovine; D006433:Hemocyanins; D012999:Soman