Identification of Three Highly Attenuated Salmonella typhimurium Mutants That Are More Immunogenic and Protective in Mice than a Prototypical aroA Mutant

ABSTRACT A panel of Salmonella typhimurium 14028s mutants, which were previously shown to be highly attenuated in the BALB/c mouse model of infection, were analyzed for their potential as liveSalmonella oral-vaccine candidates. A prototypicalaroA mutant was chosen as a basis of comparison. From the panel of mutants initially chosen for this study, three mutants with comparable levels of attenuation elicited higherSalmonella-specific serum immunoglobulin G (IgG) and/or mucosal secretory-IgA antibody titers than the aroA vaccine strain. The three mutants, CL288, CL401, and CL554, also elicited a better protective immune response than the aroA control strain, after a single oral dose of 1 × 109 to 2 × 109 bacteria.

[1]  E. Groisman,et al.  At Least Four Percent of the Salmonella typhimurium Genome Is Required for Fatal Infection of Mice , 1998, Infection and Immunity.

[2]  N. W. Davis,et al.  The complete genome sequence of Escherichia coli K-12. , 1997, Science.

[3]  G. Dougan,et al.  Safety of live oral Salmonella typhi vaccine strains with deletions in htrA and aroC aroD and immune response in humans , 1997, Infection and immunity.

[4]  S. Miller,et al.  phoP/phoQ-deleted Salmonella typhi (Ty800) is a safe and immunogenic single-dose typhoid fever vaccine in volunteers. , 1996, The Journal of infectious diseases.

[5]  F. Heffron,et al.  Induction of SIV capsid-specific CTL and mucosal sIgA in mice immunized with a recombinant S. typhimurium aroA mutant. , 1996, Vaccine.

[6]  B. Rouse,et al.  Differential induction of carrier antigen-specific immunity by Salmonella typhimurium live-vaccine strains after single mucosal or intravenous immunization of BALB/c mice , 1995, Infection and immunity.

[7]  J. Shea,et al.  Simultaneous identification of bacterial virulence genes by negative selection. , 1995, Science.

[8]  F. Blattner,et al.  Analysis of the Escherichia coli genome VI: DNA sequence of the region from 92.8 through 100 minutes. , 1995, Nucleic acids research.

[9]  G. Dougan,et al.  Live Salmonella vaccines as a route towards oral immunisation. , 1995, Biologicals : journal of the International Association of Biological Standardization.

[10]  M. Marinaro,et al.  Mucosal immunity to infection with implications for vaccine development. , 1994, Current opinion in immunology.

[11]  F. Heffron,et al.  Salmonella typhimurium loci involved in survival within macrophages , 1994, Infection and immunity.

[12]  MJ Mahan,et al.  Selection of bacterial virulence genes that are specifically induced in host tissues , 1993, Science.

[13]  E. Groisman,et al.  Resistance to host antimicrobial peptides is necessary for Salmonella virulence. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[14]  M. Levine,et al.  Comparison of the safety and immunogenicity of delta aroC delta aroD and delta cya delta crp Salmonella typhi strains in adult volunteers , 1992, Infection and immunity.

[15]  I. Charles,et al.  Evaluation of Salmonella typhimurium strains harbouring defined mutations in htrA and aroA in the murine salmonellosis model. , 1992, Microbial pathogenesis.

[16]  B. Finlay,et al.  Intracellular replication is essential for the virulence of Salmonella typhimurium. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Dougan,et al.  Construction of genetically defined double aro mutants of Salmonella typhi. , 1991, Vaccine.

[18]  S. Miller,et al.  Salmonella vaccines with mutations in the phoP virulence regulon. , 1990, Research in microbiology.

[19]  M. Levine,et al.  Clinical and field trials with attenuated Salmonella typhi as live oral vaccines and as "carrier" vaccines. , 1990, Research in microbiology.

[20]  G. Dougan,et al.  Characterization of porin and ompR mutants of a virulent strain of Salmonella typhimurium: ompR mutants are attenuated in vivo , 1989, Infection and immunity.

[21]  B. Stocker,et al.  Effect of a purA mutation on efficacy of Salmonella live-vaccine vectors , 1989, Infection and immunity.

[22]  J. Galán,et al.  Virulence and vaccine potential of phoP mutants of Salmonella typhimurium. , 1989, Microbial pathogenesis.

[23]  B. Finlay,et al.  Common themes in microbial pathogenicity , 1989, Microbiological reviews.

[24]  G. Dougan,et al.  Construction and characterization of vaccine strains of Salmonella harboring mutations in two different aro genes. , 1988, The Journal of infectious diseases.

[25]  G. Dougan,et al.  Identification and characterization of TnphoA mutants of Salmonella that are unable to pass through a polarized MDCK epithelial cell monolayer , 1988, Molecular microbiology.

[26]  G. Dougan,et al.  Characterization of aromatic- and purine-dependent Salmonella typhimurium: attention, persistence, and ability to induce protective immunity in BALB/c mice , 1988, Infection and immunity.

[27]  R. Curtiss,et al.  Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic , 1987, Infection and immunity.

[28]  R. Black,et al.  LARGE-SCALE FIELD TRIAL OF TY21A LIVE ORAL TYPHOID VACCINE IN ENTERIC-COATED CAPSULE FORMULATION , 1987, The Lancet.

[29]  C. Haidaris,et al.  Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[30]  R. Germanier,et al.  Isolation and characterization of Gal E mutant Ty 21a of Salmonella typhi: a candidate strain for a live, oral typhoid vaccine. , 1975, The Journal of infectious diseases.

[31]  L. Reed,et al.  A SIMPLE METHOD OF ESTIMATING FIFTY PER CENT ENDPOINTS , 1938 .

[32]  K. Isono,et al.  Construction of a contiguous 874-kb sequence of the Escherichia coli -K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features. , 1997, DNA research : an international journal for rapid publication of reports on genes and genomes.

[33]  S. Miller,et al.  Evaluation of a phoP/phoQ-deleted, aroA-deleted live oral Salmonella typhi vaccine strain in human volunteers. , 1996, Vaccine.

[34]  F. Schödel,et al.  Salmonellae as oral vaccine carriers. , 1995, Developments in biological standardization.

[35]  M. Levine,et al.  Recombinant Salmonella vectors in vaccine development. , 1994, Developments in biological standardization.

[36]  M. Levine,et al.  Clinical acceptability and immunogenicity of CVD 908 Salmonella typhi vaccine strain. , 1992, Vaccine.