Conjugation of isometamidium chloride to antibodies and the use of theconjugate against the haemoflagellate, Cryptobia salmositica Katz, 1951:an immuno-chemotherapeutic strategy

摘要

The trypanocidal drug isometamidium chloride (Samorin) was conjugated to polyclonal and monoclonal antibodies produced against the pathogenic haemoflagellate Cryptobia salmositica. Under in vitro conditions the unconjugated drug normally accumulates rapidly in the kinetoplast in the parasite; however, once it was conjugated to antibodies (either polyclonal or monoclonal) it was found throughout the parasite. Isometamidium conjugated to polyclonal antibodies lyse C salmositica under in vitro conditions, but parasites were not agglutinated. In contrast, isometamidium conjugated to monoclonal antibodies (against a 200 kDa surface membrane glycoprotein) did not lyse C salmositica, but parasites were agglutinated. Because of the low efficacy of the monoclonal conjugate against the parasite in vitro, its cryptobiocidal effect was not evaluated further. The infectivity of C salmositica (incubated either in culture medium or whole blood) was reduced in fish after in vitro exposure to isometamidium conjugated to polyclonal antibodies. Parasitaemias were reduced in infected chinook salmon, Oncorhynchus tshawytscha, after treatment with isometamidium conjugated to polyclonal antibodies.