Aromatic-dependent Salmonella typhimurium as modified live vaccines for calves

Abstract

SUMMARY Strains of Salmonella sp with complete nonreverting aromatic biosynthesis ( aro ) defects are expected to be nonvirulent, in respect to invasive infection, because they need the aromatic metabolites paraaminobenzoate (for making folate) and dihydroxybenzoate (for making enterochelin) which are not available in host tissues. Derivatives with transposon-generated complete nonreverting aro − defects were prepared from 3 mouse-virulent strains of S typhimurium , namely, FIRN, WRAY, and UCD. The latter 2 parent strains originally were isolated from calves and are known to be calf-virulent. The resultant aromatic-dependent ( aro − ) strains were used to vaccinate 27 calves (2 to 3 weeks old), usually giving 2 doses by the im route (10 9 bacteria) or orally (1.5 × 10 11 ). Vaccination did not cause severe ill effects in any calf. Thus aro − defects cause loss of virulence for calves, as previously shown for mice. Vaccinated and control calves were challenge exposed, usually at 5 weeks of age, by feeding 1.5 × 10 11 cells of 1 of 2 calf-virulent S typhimurium strains, either UCD 108-11 or SL1323. Of the 16 challenge-exposed control calves, all became anorectic and depressed ( cns ), and 15 had diarrhea. Fourteen of the 16 died; all tested tissues were bacteriologically culture-positive for Salmonella at necropsy. Vaccination with the live UCD aro − vaccine strain, SL1479 by either of 2 schedules ( im or orally) appeared effective. Six of the 7 calves vaccinated with 2 im doses of strain SL1479 survived challenge exposure (4 of the 7 not even developing diarrhea), and all of 3 calves which had been vaccinated with 2 oral doses of the live UCD vaccine also survived challenge exposure. In contrast, 3 calves which had been given 1 im dose and then the oral dose of strain SL1479 were not protected—2 of them dying after challenge exposure. The other aro − strains (FIRN and WRAY) proved ineffective or relatively ineffective as live-organism vaccines, at least with the schedules tested. Failure of the FIRN aro − vaccine may reflect the organism's origin from a wild strain which, though mice-virulent, was of a bio type seldom isolated from cattle and perhaps not well adapted for persistence in bovine tissues. There is no reason that can be suggested for the vaccinal failure of 2 oral doses of the WRAY aro − strain. Thus one aro − live bacterial vaccine, the S typhimurium UCD aro − strain SL1479, given im (2 doses) or orally (2 doses), did not cause significant side effects and prevented death or severe illness in challenge exposed calves.