Virus-neutralizing monoclonal antibody expressed in milk of transgenic mice provides full protection against virus-induced encephalitis

Andreas Kolb, L Pewe, John Webster, S Perlman, C B A Whitelaw, S G Siddell

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    25 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)2803-2809
    Number of pages7
    JournalJournal of General Virology
    Volume75
    Issue number6
    DOIs
    Publication statusPublished - Mar 2001

    Keywords

    • mouse hepatitis-virus
    • ovine beta-lactoglobulin
    • MHV-JHM
    • coronavirus infection
    • passive protection
    • bovine colostrum
    • neonatal mice
    • immunity
    • receptor
    • encephalyomyelitis

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