We describe a regulated antigen delivery system (RADS) that has (a) a
vector that includes (1) a gene encoding a desired gene product operably
linked to a control sequence, (2) an origin of replication conferring
vector replication using DNA polymerase III, and (3) an origin of
replication conferring vector replication using DNA polymerase I, where
the second origin of replication is operably linked to a control sequence
that is repressible by a repressor. The RADS microorganism also has a
gene encoding a repressor, operably linked to an activatible control
sequence. The RADS described provide high levels of the desired gene
product after repression of the high copy number origin of replication is
lifted. The RADS are particularly useful as live bacterial vaccines. Also
described is a delayed RADS system, in which there is a delay before the
high copy number origin is expressed after the repression is lifted. The
delayed RADS is also particularly useful for live bacterial vaccines.
Also described are several control elements useful for these systems, as
well as methods for providing immunity to a pathogen in a vertebrate
immunized with the RADS microorganisms.