ENGINEERING PASSIVE-IMMUNITY IN TRANSGENIC MICE SECRETING VIRUS-NEUTRALIZING ANTIBODIES IN MILK

Protection against enteric infections can be provided by the oral admi nistration of pathogen-neutralizing antibodies. To provide passive imm unity, 18 lines of transgenic mice secreting a recombinant monoclonal antibody (Mab) neutralizing transmissible gastroenteritis coronavirus (TGEV) into the milk were generated. The genes encoding a chimeric Mab with the variable modules of the murine TGEV-specific Mab 6A.C3 and t he constant modules of a human IgG(1) isotype Mab were expressed under the control of regulatory sequences derived from the whey acidic prot ein, which is an abundant milk protein. The Mab 6A.C3 binds to a highl y conserved epitope present in coronaviruses of several species, which does not allow the selection of neutralization escape mutants. Antibo dy expression titers of 10(6) were obtained in the milk of transgenic mice that reduced TGEV infectivity 10(6)-fold. The antibody was synthe sized at high levels throughout lactation. Integration of matrix attac hment region sequences with the antibody genes red to a 20- to 10,000- fold increase in the antibody titer in 50% of the transgenic animals. Antibody expression levels were transgene copy number independent and related to the site of integration. The generation of transgenic anima ls producing virus neutralizing antibodies in milk could provide an ap proach to protection against neonatal infections of the enteric tract.