AROMATIC-DEPENDENT SALMONELLA AS LIVE VACCINE PRESENTERS OF FOREIGN EPITOPES AS INSERTS IN FLAGELLIN

Synthetic oligonucleotides specifying amino acid sequences identified as epitopes of various foreign antigens (cholera toxin subunit B, hepatitis B surface protein and others) have been inserted at an EcoRV-EcoRV deletion site in a cloned Salmonella flagellin gene; the resulting plasmids, when placed in flagellin-negative Escherichia coli or Salmonella sp. strains, caused production of flagellin expressing the epitope. If the chimeric flagellin allowed formation of flagella, the epitope was exposed at the surface of the flagellar filaments. A DELTA-aroA flagellin-negative S. dublin live vaccine strain given plasmids carrying various chimeric flagellin genes was administered to mice, etc. Serum antibody specific for the foreign epitope was in all cases evoked by parenteral administration; oral route administration was effective in the case of two epitopes of hepatitis B surface protein but not effective for several other epitopes. Several i.p. inocula of the live vaccine strain with an insert corresponding to the 15 N-terminal amino acids of the M protein of Streptococcus pyogenes type 5 evoked M-specific antibody with opsonic activity, and the mice were (incompletely) protected against a lethal challenge of S. pyogenes type 5.