Transgenic Research

, Volume 18, Issue 3, pp 445–453

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

Authors

  • Ran Zhang
    • State Key Laboratory of AgrobiotechnologyChina Agricultural University
  • Man Rao
    • State Key Laboratory of AgrobiotechnologyChina Agricultural University
  • Chuan Li
    • State Key Laboratory for Infectious Disease Control and PreventionNational Institute for Viral Diseases Control and Prevention, China CDC
  • Jingyuan Cao
    • State Key Laboratory for Infectious Disease Control and PreventionNational Institute for Viral Diseases Control and Prevention, China CDC
  • Qinglin Meng
    • State Key Laboratory for Infectious Disease Control and PreventionNational Institute for Viral Diseases Control and Prevention, China CDC
  • Min Zheng
    • Beijing Genprotein Biotechnology Company
  • Meili Wang
    • Beijing Genprotein Biotechnology Company
  • Yunping Dai
    • State Key Laboratory of AgrobiotechnologyChina Agricultural University
    • State Key Laboratory for Infectious Disease Control and PreventionNational Institute for Viral Diseases Control and Prevention, China CDC
    • State Key Laboratory of AgrobiotechnologyChina Agricultural University
Original Paper

DOI: 10.1007/s11248-008-9241-0

Cite this article as:
Zhang, R., Rao, M., Li, C. et al. Transgenic Res (2009) 18: 445. doi:10.1007/s11248-008-9241-0

Abstract

Hepatitis A virus (HAV) is a wide spread pathogenic agent and is the common cause of acute Hepatitis A worldwide. Passive immunization of HAV plays an extremely important role in post-exposure prophylaxis with clinical applications often requiring large amounts of antibody. As an alternative to the in vitro production of recombinant proteins, expression of monoclonal antibodies (mAbs) in the milk of transgenic animals is currently used being associated with low production costs and high activity. In this paper, eight founder lines of transgenic mice were generated by co-microinjection of the two cassettes encoding the heavy- and light-chains of a neutralizing anti-HAV antibody, respectively. The expressed heavy- and light-chains of the mAb were correctly assembled and modified in the mammary gland as detected by western blotting. High expression levels of the antibody were achieved during the lactation period and found to be independent of the copy numbers of integrated transgenes. The highest level was up to 32.2 mg/ml. The binding specificity and neutralizing activity of the expressed mAb were assayed by ELISA and neutralizing test, showing that it is capable to neutralize the JN strain of Hepatitis A virus efficiently. Therefore, our results suggest that a large-scale and efficient production of the anti-HAV mAb in the milk of transgenic farm animals would be feasible in the future.

Keywords

Hepatitis A virusMonoclonal antibodyTransgenic miceMilk

Copyright information

© Springer Science+Business Media B.V. 2009