TY - JOUR
T1 - Immunology and immunopathology of the intestines
T2 - Recombinant avirulent salmonella vaccine strains with stable maintenance and High level expression of cloned genes in vivo
AU - Curtiss, Roy
AU - Nakayama, Koji
AU - Kelly, Sandra M.
N1 - Funding Information:
We thank Claudia Gentry-Weeks, Raul Goldschmidt, David Howe, Michael Hudson, and Steven Tinge for helpful suggestions on preparation and content of this manuscript. This work was supported by Public Health Service grants DE06659 and DE06673 from the National Institute of Dental Research.
PY - 1989
Y1 - 1989
N2 - Salmonella typhimurium strains with deletion (Δ of the adenylate cyclase (cya) and cyclic AMP receptor protein (crp) genes are avirulent for mice and induce a high level of protective immunity to oral challenge with up to 10,000 times what would be a lethal dose of wild-type virulent S. typhimurium cells. This immunity begins as early as seven days after immunization and lasts for at least four months. S. typhimurium Δcya Δcrp mutants stably maintain plasmids and give high-level expression of cloned gene products; in this they appear superior to other avirulent S. typhimurium strains. S. typhimurium Δcya Δcrp strains with a Δasd mutation (abolishing production of aspartate βsemialdehyde dehydrogenase), have an obligate requirement for diaminopimelic acid (DAP). This strain can be used in conjunction with plasmid vectors lacking antibiotic resistance markers but having the wildtype asd+ gene from Streptococcus mutans to complement the Δasd chromosomal mutation. The Asd+ plasmid vector can be used to express a diversity of colonization and virulence antigens from other pathogens. In the Δcya Δcrp Δasd S. typhimurium vaccine strain, the plasmid is completely stable in the absence of any exogenous selective pressure either in vitro or in vivo.
AB - Salmonella typhimurium strains with deletion (Δ of the adenylate cyclase (cya) and cyclic AMP receptor protein (crp) genes are avirulent for mice and induce a high level of protective immunity to oral challenge with up to 10,000 times what would be a lethal dose of wild-type virulent S. typhimurium cells. This immunity begins as early as seven days after immunization and lasts for at least four months. S. typhimurium Δcya Δcrp mutants stably maintain plasmids and give high-level expression of cloned gene products; in this they appear superior to other avirulent S. typhimurium strains. S. typhimurium Δcya Δcrp strains with a Δasd mutation (abolishing production of aspartate βsemialdehyde dehydrogenase), have an obligate requirement for diaminopimelic acid (DAP). This strain can be used in conjunction with plasmid vectors lacking antibiotic resistance markers but having the wildtype asd+ gene from Streptococcus mutans to complement the Δasd chromosomal mutation. The Asd+ plasmid vector can be used to express a diversity of colonization and virulence antigens from other pathogens. In the Δcya Δcrp Δasd S. typhimurium vaccine strain, the plasmid is completely stable in the absence of any exogenous selective pressure either in vitro or in vivo.
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U2 - 10.3109/08820138909112265
DO - 10.3109/08820138909112265
M3 - Article
C2 - 2659521
AN - SCOPUS:0024513781
SN - 0882-0139
VL - 18
SP - 583
EP - 596
JO - Immunological Investigations
JF - Immunological Investigations
IS - 1-4
ER -