Dev Biol Stand. 1983;53:47-54.
Aromatic-dependent "Salmonella sp." as live vaccine in mice and calves.
Developments in biological standardization
B A Stocker, S K Hoiseth, B P Smith
PMID: 6307785
Abstract
A block in the common aromatic biosynthesis (aro) pathway makes E. coli, Salmonella, etc., exacting for aromatic metabolites; two of these, paraaminobenzoic acid and dihydroxybenzoic acid, are not mammalian metabolites. Bacteria needing substances not available in host tissues should be unable to grow there and so be non-virulent. Transposon-generated deletion and deletion-inversion mutations at aroA caused loss of mouse virulence in Salmonella typhimurium; e.g., LD50, intraperitoneal route, increased from less than 10 to greater than 10(6), and LD50 by feeding increased from ca. 10(5) to greater than 10(8). Furthermore, a single injection of 10(5) live aro- bacteria protected mice of a Salmonella-susceptible line, BALB/c, against challenge, 4 weeks later, with 5 X 10(5) virulent S. typhimurium (i.e., greater than 10(4) LD50); a single dose of the live-vaccine strain given i.p. also protected against challenge one month later by feeding 2 X 10(7) of a virulent strain. Mice vaccinated by feeding 2 X 10(8) live aro- bacteria were unaffected by feeding, one month later, 2 X 10(7) of a virulent S. typhimurium strain ( = ca 100 LD50). Intravenous injection of microparticulate silica did not reduce the mouse i.p. LD50 of an aro- strain, and 3 i.p. injections of cyclophosphamide, 4 mgm, caused only a small reduction. Thus the reduced virulence of the aro- strain does much depend on the integrity of host cellular defense mechanisms. Non-reverting aro- derivatives made from proven calf-virulent S. typhimurium and S. dublin strains are being tested at the School of Veterinary Medicine, University of California at Davis. None of 26 calves given aro- live-vaccine bacteria intramuscularly (usually 10(9)) and none of 8 calves fed ca. 10(11) live aro- bacteria, died or became seriously ill. Vaccinated and control calves were challenged by feeding 10(11) bacteria of a virulent strain, S. typhimurium or S. dublin. This challenge caused death of 14 of 16 non-vaccinated calves. The results, to date, in vaccinated animals indicate that one aro- strain of each of the two Salmonella species is effective if given as a live vaccine in two intramuscular doses.
Cited by
Riquelme S, Varas M, Valenzuela C, Velozo P, Chahin N, Aguilera P, Sabag A, Labra B, Álvarez SA, Chávez FP, Santiviago CA.
Front Microbiol. 2016 Aug 23;7:1305. doi: 10.3389/fmicb.2016.01305. eCollection 2016.
PMID: 27602025
Substances
MeSH terms
Publication Types
Grant support