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Journal of Virology, March 2001, p. 2803-2809, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.2803-2809.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Virus-Neutralizing Monoclonal Antibody Expressed in Milk of Transgenic Mice Provides Full Protection against Virus-Induced Encephalitis

Andreas F. Kolb,1,2,* Lecia Pewe,3 John Webster,4 Stanley Perlman,3 C. Bruce A. Whitelaw,4 and Stuart G. Siddell2

Cell Physiology Group, Hannah Research Institute, Ayr,1 and Department of Gene Expression and Development, Roslin Institute, Roslin,4 United Kingdom; Institute of Virology, University of Würzburg, Würzburg, Germany2; and Department of Pediatrics and Microbiology, University of Iowa, Iowa City, Iowa3

Received 14 August 2000/Accepted 8 December 2000

Neutralizing antibodies represent a major host defense mechanism against viral infections. In mammals, passive immunity is provided by neutralizing antibodies passed to the offspring via the placenta or the milk as immunoglobulin G and secreted immunoglobulin A. With the long-term goal of producing virus-resistant livestock, we have generated mice carrying transgenes that encode the light and heavy chains of an antibody that is able to neutralize the neurotropic JHM strain of murine hepatitis virus (MHV-JHM). MHV-JHM causes acute encephalitis and acute and chronic demyelination in susceptible strains of mice and rats. Transgene expression was targeted to the lactating mammary gland by using the ovine beta -lactoglobulin promoter. Milk from these transgenic mice contained up to 0.7 mg of recombinant antibody/ml. In vitro analysis of milk derived from different transgenic lines revealed a linear correlation between antibody expression and virus-neutralizing activity, indicating that the recombinant antibody is the major determinant of MHV-JHM neutralization in murine milk. Offspring of transgenic and control mice were challenged with a lethal dose of MHV-JHM. Litters suckling nontransgenic dams succumbed to fatal encephalitis, whereas litters suckling transgenic dams were fully protected against challenge, irrespective of whether they were transgenic. This demonstrates that a single neutralizing antibody expressed in the milk of transgenic mice is sufficient to completely protect suckling offspring against MHV-JHM-induced encephalitis.

* Corresponding author. Mailing address: Cell Physiology Group, Hannah Research Institute, Ayr, KA6 5HL Scotland, United Kingdom. Phone: 44-1292-674020. Fax: 44-1292-674003. E-mail: kolba{at}hri.sari.ac.uk.

Journal of Virology, March 2001, p. 2803-2809, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.2803-2809.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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