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

Neutralizing antibodies represent a major host defense mechanism against vi ral infections. In mammals, passive immunity is provided by neutralizing an tibodies passed to the offspring via the placenta or the milk as immunoglob ulin 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 ca uses acute encephalitis and acute and chronic demyelination in susceptible strains of mice and rats. Transgene expression was targeted to the lactatin g 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 activ ity, indicating that the recombinant antibody is the major determinant of M HV-JHM neutralization in murine milk. Offspring of transgenic and control m ice were challenged with a lethal dose of MHV-JHM. Litters suckling nontran sgenic dams succumbed to fatal encephalitis, whereas litters suckling trans genic 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 prote ct suckling offspring against MHV-JHM-induced encephalitis.