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)%tDAvQAPD93ӗX㔓*I+;ޞ+^ILx-s*R*Jx^ ^xk㭩jR/{]0ǒfĕk#^JLB@)#Hg';P!G*UQ!³DWxx5g X\o#e]}QtڃdUT]}[d[!F&xN-u^/wzeO^{@-R+dQ*R_R SD^=7*Q%|L D3ȗT1Q$Yښ;mOՍҺ%^!RSJ}(ad 'JKNoݓoy= u!.R;r( 묺"ʿ(^(L32:|bW}q}K?4KdGwzO.6ڿYUZBwBz;<KZ#PZ"ɒоzwƦl8IvJ5z|ZP@gуY/ogOU܎U1$H #9@0Rșg K9}YH #- Roa 9l90RHËP%QduFj9k?; 0 endstream endobj 347 0 obj <>stream h엽7 _Eop+iHa HƈKE4&xHl8ۈZ5 o6fiV-tXk}1ckaoom{pξjL7y5s4_s絵u`[64N_ s<[-xJ o o x3 <.IxV+,Ię8:*҅H"]4!Qr3<3<#mfA1pQIgYd}b5\8IMnRujT'U? n"2.#XIWu&.I5LaRETߤJ'U:IN|MjtFҭ%Z]&]^>tIL̄ɤkK(NHK̈́IL x x7l~']c=]eЍ<<]Kе]Oz|Ǡ ׀׀׀Ϡ x x x π+ Qsg1w֣s=1^!*WE6Ax+6{{䬬;X+tYYm,XAQWІ/>'V@W]/1|KQ endstream endobj 348 0 obj <> endobj 349 0 obj <> endobj 350 0 obj <>stream application/pdf Therapeutic Monoclonal Antibodies andtheir Engineered Antibody FragmentsSpecific to Lipl32 for Passive Immunotherapyof 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. © 2016 Maneewatchararangsri S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Santi Maneewatchararangsri* Leptospirosis Re-emerging zoonosis Passive immunotherapy Therapeutic monoclonal antibody LipL32 2016-06-30T14:22:11+05:30 2016-06-30T14:22:12+05:30 2016-06-30T14:22:12+05:30 4 Adobe InDesign CS6 (Windows) uuid:df9828c8-5c50-47e4-a976-0890026d8bf7 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:B020B98E9F3EE61199449B81D5FAE482 proof:pdf xmp.iid:3E2FDCC6893EE611BBFFE7F5D2815DD7 xmp.did:596E10D992C8E411A9F7BE0811E790A6 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2016-06-30T14:22:11+05:30 Citation: Maneewatchararangsri S (2016)Therapeutic Monoclonal Antibodies and TheirEngineered Antibody Fragments Specific to Lipl32for Passive Immunotherapy of Leptospirosis. JVirol Emerg Dis 2(2): doi http://dx.doi.org/10.16966/jved.114 Santi Maneewatchararangsri, Department of Molecular Tropical Medicineand Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand, Tel:+66 2306 9100 Ext. 2035; Fax: +66 2306 9139; E-mail: santi.man@mahidol.ac.th Adobe PDF Library 10.0.1 False endstream endobj 351 0 obj <> endobj xref 0 1079 0000000000 65535 f 0000273910 00000 n 0000274454 00000 n 0000274478 00000 n 0000283146 00000 n 0000283268 00000 n 0000283351 00000 n 0000286516 00000 n 0000286885 00000 n 0000304288 00000 n 0000304540 00000 n 0000336072 00000 n 0000336109 00000 n 0000336185 00000 n 0000336466 00000 n 0000337572 00000 n 0000368844 00000 n 0000368904 00000 n 0000369363 00000 n 0000370263 00000 n 0000370398 00000 n 0000380414 00000 n 0000380499 00000 n 0000380559 00000 n 0000380992 00000 n 0000381177 00000 n 0000381312 00000 n 0000383692 00000 n 0000383777 00000 n 0000383837 00000 n 0000383922 00000 n 0000384535 00000 n 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application/pdf Therapeutic Monoclonal Antibodies andtheir Engineered Antibody FragmentsSpecific to Lipl32 for Passive Immunotherapyof 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. © 2016 Maneewatchararangsri S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Santi Maneewatchararangsri* Leptospirosis Re-emerging zoonosis Passive immunotherapy Therapeutic monoclonal antibody LipL32 2016-06-30T14:22:11+05:30 2016-06-30T14:22:16+05:30 2016-06-30T14:22:16+05:30 4 Adobe InDesign CS6 (Windows) uuid:8c12253d-669b-44d4-9740-c78049a7ffac xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:B020B98E9F3EE61199449B81D5FAE482 proof:pdf xmp.iid:3E2FDCC6893EE611BBFFE7F5D2815DD7 xmp.did:596E10D992C8E411A9F7BE0811E790A6 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2016-06-30T14:22:11+05:30 Citation: Maneewatchararangsri S (2016)Therapeutic Monoclonal Antibodies and TheirEngineered Antibody Fragments Specific to Lipl32for Passive Immunotherapy of Leptospirosis. JVirol Emerg Dis 2(2): doi http://dx.doi.org/10.16966/jved.114 Santi Maneewatchararangsri, Department of Molecular Tropical Medicineand Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand, Tel:+66 2306 9100 Ext. 2035; Fax: +66 2306 9139; E-mail: santi.man@mahidol.ac.th Adobe PDF Library 10.0.1 False endstream endobj 351 0 obj <> endobj 1080 0 obj <>/Metadata 350 0 R/Names 1081 0 R/Outlines 325 0 R/PageMode/UseOutlines/Pages 349 0 R/StructTreeRoot 352 0 R/Type/Catalog/ViewerPreferences<>>> endobj xref 0 1 0000000000 65535 f 350 2 0000519461 00000 n 0000527695 00000 n 1080 1 0000529643 00000 n trailer <<5B7765ACCB203449A7B7B6EBDAF29207>]/Prev 116>> startxref 529847 %%EOF