An attenuated strain of S. typhimurium has been used as a vehicle for
oral genetic immunization. Eukaryotic expression vectors containing tr
uncated genes of ActA and listeriolysin-two virulence factors of Liste
ria monocytogenes-have been used to transform S. typhimurium aroA. Mul
tiple or even single oral immunizations with such transformants induce
d excellent cellular and humoral responses. In addition, protective im
munity was induced with listeriolysin transformants. The quality of th
e responses suggested a transfer of plasmid DNA from the bacterial car
rier to the host. Such transfer was unequivocally shown in vitro with
primary peritoneal macrophages. We describe a highly versatile system
for antigen delivery, identification of protective antigens for vaccin
ation, and efficient generation of antibodies against the product of o
pen reading frames present on virtually any DNA segment.