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PEDS Advance Access originally published online on March 18, 2009
Protein Engineering Design and Selection 2009 22(5):305-312; doi:10.1093/protein/gzp008
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Humanized-monoclonal antibody against heterologous Leptospira infection

Santi Maneewatch1, Yuwaporn Sakolvaree1, Pramuan Tapchaisri1, Patcharin Saengjaruk2, Thaweesak Songserm3, Surasakdi Wongratanachewin4, Pongsri Tongtawe1, Potjanee Srimanote1, Urai Chaisri5 and Wanpen Chaicumpa6,7

1Graduate Program, Faculty of Allied Health Sciences, Thammasat University, Rangsit Center, Pathum-thani 12120, Thailand 2Department of Pathology, Faculty of Medicine Srinakharinwirot University, Bangkok, Thailand 3Department of Pathology, Faculty of Veterinary Medicine, Kasetsart University, Kam paeng-saen Campus, Nakhon-Pathom Province, Thailand 4Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand 5Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand 6Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand

7 To whom correspondence should be addressed. E-mail: tmwcc{at}mahidol.ac.th or tmwcc{at}yahoo.com

Patients with leptospirosis are commonly treated with antibiotics. Jarisch–Herxheimer reaction caused by toxic bacterial substances massively released as a result of the antibiotic mediated-bacterial lysis occurs in some patients which may aggravate the existing severe clinical manifestations. In this study, a humanized-murine single-chain monoclonal antibody (HuScFv) was produced and tested as an alternative of antibiotics for treatment of leptospirosis. Complementary DNA was prepared from total RNA of a murine hybridoma clone secreting monoclonal antibody (MAb) specific to LipL32 of pathogenic Leptospira spp. The MAb had therapeutic efficacy in Leptospira challenged hamsters. The VH and VL coding sequences were amplified using the cDNA as a template. The sequences were linked to form a single-chain variable murine DNA fragment (muscFv). CDR sequences of the muscFv were grafted onto the best matching human VH and VL immunoglobulin frameworks. After cloning of the humanized murine DNA sequences (huscFv) into a phagemid vector and the vector was introduced into competent Escherichia coli, the HuScFv was produced. On the same weight basis, the HuScFv possessed equal neutralizing activities to the murine ScFv counterpart against heterologous Leptospira-mediated hemolysis in vitro and rescued hamsters from a heterologous Leptospira lethal challenge. The HuScFv antibody has high therapeutic potential as an alternative to antibiotics for human leptospirosis, especially for drug hypersensitive patients.

Keywords: immunology/immunotherapy

Received November 4, 2008; revised November 4, 2008; accepted February 23, 2009.


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