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Functional recombinant human anti-HBV antibody expressed in milk of transgenic mice

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Abstract

Anti-HBV monoclonal antibodies (mAbs) have been successfully applied in clinic for the prevention and treatment of liver diseases caused by Hepatitis B virus (HBV). However, the mammalian cell culture technique used to produce mAbs provides low yield. Production capacity may be increased by manipulating the mammary gland of transgenic animals to produce mAbs which may be secreted in the milk and readily purified. In this study, we established a transgenic mouse model expressing anti-HBV mAbs and assessed the quantity and quality of such in milk secretions. Eight transgenic founders were generated by co-microinjection of two gene cassettes encoding the heavy- and light-chain of a neutralizing anti-HBV antibody. Both the heavy- and light-chain transgenes produced sufficient transcript expression in the transgenic mice. The expressed anti-HBV mAb was correctly assembled and modified in the mammary gland, as detected by western blotting. ELISA was used to determine the expression level of anti-HBV mAb, which reached up to 17.8 mg/mL, and the affinity of anti-HBV mAb for HBV surface antigen HBsAg, which reached up to 1,577 IU/mg. Therefore, our work confirms the concept of using transgenic animals for large-scale production of therapeutic anti-HBV mAb.

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Acknowledgments

This study was supported by a grant from the Chinese Universities Scientific Fund (2009-1-75).

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Correspondence to Mifang Liang or Ning Li.

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Zhang, R., Cui, D., Wang, H. et al. Functional recombinant human anti-HBV antibody expressed in milk of transgenic mice. Transgenic Res 21, 1085–1091 (2012). https://doi.org/10.1007/s11248-012-9589-z

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