Therapeutic Monoclonal Antibodies and their Engineered Antibody Fragments Specific to LipL32 for Passive Immunotherapy of Leptospirosis

Leptospirosis is a globally re-emerging neglected zoonotic disease that continues to be a significant human and veterinary public health concerns, with 0.1-1/100,000 population and estimated 350,000-500,000 severe cases annually (International Leptospirosis Society surveys). The disease is caused by infections of pathogenic spirochetes of the genus Leptospira which are classified into 20 genomospecies and placed more than 250 serovars/strains. Treatment by antibiotics such as doxycycline, ceftriaxone, azithomycin is predominant. Antibiotics provide therapeutic activity when initiated early of illness, and might be less effective at late and severe of human leptospirosis such as Weil's disease and severe pulmonary hemorrhagic syndrome and also in animal reservoirs. Besides, antibiotics might cause adverse effects, i.e., Jarisch-Herxheimer reaction, due to massive release of the bacterial toxic substances. An immunomodulation or passive immunotherapy by using therapeutic antibodies against the Leptospira virulent factors might be the optimal therapeutic approach for the late and severe leptospirosis. LipL32, an immunodominant outer membrane protein of pathogenic Leptospira spp. has been used as diagnostic biomarker, vaccine candidate for a broad spectrum vaccine development, and therapeutic target for passive immunotherapy of leptospirosis. Passive immunotherapy of experimental leptospirosis by using therapeutic mouse monoclonal antibodies and their single-chain variable fragment antibodies specific to LipL32 have been demonstrated.