The authors have designed and constructed a plantoptimized synthetic gene encoding the Escherichia coli heatlabile enterotoxin B subunit (LTB), for use in transgenic plants as a edible vaccine against enterotaxigenic E. coli. Expression of the synthetic LTB gene in potato plants under the control of a constitutive promoter yielded increased accumulation of LTB in leaves and tubers, as compared to the bacterial LTB gene. The plantderived LTB assembled into native pentameric structures as evidenced by its ability to bind gangliaside. The authors demonstrated immunogenicity by feeding mice the raw tubers and comparing the antiLTB serum IgG and faecal IgA to that produced in mice gavaged with bacterial LTB. Mice were fed three weekly doses of 5 g tuber tissue containing either 20 or 50 ug LTB, or gavaged weekly with 5 ug of LTB from recombinant E. coli. One week after the third dose, mice immunized with potato LTB had higher levels of serum and mucosal antiLTB than those gavaged with bacterial LTB had higher levels of serum and mucosal antiLTB than those gavaged with bacterial LTB. Mice were challenged by oral administration of 25 ug LT, and protection assessed by comparing the gutlacreass mass ratios. Although none of the mice were completely protected, the higher does potato vaccine compared favourably with the bacterial vaccine. These findings show that an edible vaccine against E. coli LTB is feasible © 1998 Elsevier Science Ltd. All rights reserved.