This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tacket, C. O.
Right arrow Articles by Levine, M. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tacket, C. O.
Right arrow Articles by Levine, M. M.

 Previous Article  |  Next Article 

Infect. Immun., Feb 1997, 452-456, Vol 65, No. 2
Copyright © 1997, American Society for Microbiology

Safety of live oral Salmonella typhi vaccine strains with deletions in htrA and aroC aroD and immune response in humans

CO Tacket, MB Sztein, GA Losonsky, SS Wasserman, JP Nataro, R Edelman, D Pickard, G Dougan, SN Chatfield and MM Levine
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA. ctacket@umppa1.ab.umd.edu

A single-dose, oral Salmonella typhi vaccine strain has been sought as a carrier or vector of cloned genes encoding protective antigens of other pathogens. Such a hybrid vaccine, administered orally, would stimulate immune responses both at the mucosal surface and in the systemic compartment and would potentially provide protection against multiple pathogens. S. typhi CVD 908 and CVD 906, which harbor deletions in aroC and aroD, were further engineered by deletion in htrA to produce strains CVD 908-htrA and CVD 906-htrA, which are unable to sustain growth and are severely impaired in their ability to survive in host tissues. These strains were fed to humans at doses of 5 x 10(7) to 5 x 10(9) CFU with buffer, and safety and immune responses were assessed. CVD 908-htrA and CVD 906-htrA were well tolerated in volunteers; mild diarrhea in 3 of 36 volunteers and mild fever in 1 volunteer were the only notable adverse responses. The vaccine strains were not detected in blood cultures and only transiently detected in stool. Serum immune responses to S. typhi lipopolysaccharide and H antigens were observed in 75 to 100% of volunteers who received 5 x 10(8) to 5 x 10(9) CFU, and cells secreting S. typhi-specific antibodies were found in all volunteers after ingestion of either strain. Sixty-three percent to 83% of volunteers developed lymphoproliferative responses to S. typhi flagellar and particulate antigens after the higher doses. These studies demonstrate the potential of CVD 908-htrA as a live vector for the delivery of heterologous genes, and a clinical trial of such a construct is planned.


This article has been cited by other articles:

  • Ramirez, K., Capozzo, A. V. E., Lloyd, S. A., Sztein, M. B., Nataro, J. P., Pasetti, M. F. (2009). Mucosally Delivered Salmonella Typhi Expressing the Yersinia pestis F1 Antigen Elicits Mucosal and Systemic Immunity Early in Life and Primes the Neonatal Immune System for a Vigorous Anamnestic Response to Parenteral F1 Boost. J. Immunol. 182: 1211-1222 [Abstract] [Full Text]  
  • Li, Y., Wang, S., Xin, W., Scarpellini, G., Shi, Z., Gunn, B., Roland, K. L., Curtiss, R. III (2008). A sopB Deletion Mutation Enhances the Immunogenicity and Protective Efficacy of a Heterologous Antigen Delivered by Live Attenuated Salmonella enterica Vaccines. Infect. Immun. 76: 5238-5246 [Abstract] [Full Text]  
  • Fang, C.-M., Wang, J. Y., Chinchilla, M., Levine, M. M., Blackwelder, W. C., Galen, J. E. (2008). Use of mchI Encoding Immunity to the Antimicrobial Peptide Microcin H47 as a Plasmid Selection Marker in Attenuated Bacterial Live Vectors. Infect. Immun. 76: 4422-4430 [Abstract] [Full Text]  
  • Sebkova, A., Karasova, D., Crhanova, M., Budinska, E., Rychlik, I. (2008). aro Mutations in Salmonella enterica Cause Defects in Cell Wall and Outer Membrane Integrity. J. Bacteriol. 190: 3155-3160 [Abstract] [Full Text]  
  • Fraillery, D., Baud, D., Pang, S. Y.-Y., Schiller, J., Bobst, M., Zosso, N., Ponci, F., Nardelli-Haefliger, D. (2007). Salmonella enterica Serovar Typhi Ty21a Expressing Human Papillomavirus Type 16 L1 as a Potential Live Vaccine against Cervical Cancer and Typhoid Fever. CVI 14: 1285-1295 [Abstract] [Full Text]  
  • Chinchilla, M., Pasetti, M. F., Medina-Moreno, S., Wang, J. Y., Gomez-Duarte, O. G., Stout, R., Levine, M. M., Galen, J. E. (2007). Enhanced Immunity to Plasmodium falciparum Circumsporozoite Protein (PfCSP) by Using Salmonella enterica Serovar Typhi Expressing PfCSP and a PfCSP-Encoding DNA Vaccine in a Heterologous Prime-Boost Strategy. Infect. Immun. 75: 3769-3779 [Abstract] [Full Text]  
  • Luo, F., Feng, Y., Liu, M., Li, P., Pan, Q., Jeza, V. T., Xia, B., Wu, J., Zhang, X.-L. (2007). Type IVB Pilus Operon Promoter Controlling Expression of the Severe Acute Respiratory Syndrome-Associated Coronavirus Nucleocapsid Gene in Salmonella enterica Serovar Typhi Elicits Full Immune Response by Intranasal Vaccination. CVI 14: 990-997 [Abstract] [Full Text]  
  • Redford, P., Welch, R. A. (2006). Role of Sigma E-Regulated Genes in Escherichia coli Uropathogenesis. Infect. Immun. 74: 4030-4038 [Abstract] [Full Text]  
  • Stephens, J. C., Darsley, M. J., Turner, A. K. (2006). Stabilization of a Plasmid Coding for a Heterologous Antigen in Salmonella enterica Serotype Typhi Vaccine Strain CVD908-htrA by Using Site-Specific Recombination. Infect. Immun. 74: 4383-4386 [Abstract] [Full Text]  
  • Talaat, A. M., Stemke-Hale, K. (2005). Expression Library Immunization: a Road Map for Discovery of Vaccines against Infectious Diseases. Infect. Immun. 73: 7089-7098 [Full Text]  
  • Galen, J. E., Zhao, L., Chinchilla, M., Wang, J. Y., Pasetti, M. F., Green, J., Levine, M. M. (2004). Adaptation of the Endogenous Salmonella enterica Serovar Typhi clyA-Encoded Hemolysin for Antigen Export Enhances the Immunogenicity of Anthrax Protective Antigen Domain 4 Expressed by the Attenuated Live-Vector Vaccine Strain CVD 908-htrA. Infect. Immun. 72: 7096-7106 [Abstract] [Full Text]  
  • Baud, D., Ponci, F., Bobst, M., De Grandi, P., Nardelli-Haefliger, D. (2004). Improved Efficiency of a Salmonella-Based Vaccine against Human Papillomavirus Type 16 Virus-Like Particles Achieved by Using a Codon-Optimized Version of L1. J. Virol. 78: 12901-12909 [Abstract] [Full Text]  
  • Kotton, C. N., Hohmann, E. L. (2004). Enteric Pathogens as Vaccine Vectors for Foreign Antigen Delivery. Infect. Immun. 72: 5535-5547 [Full Text]  
  • Li, Y., Sun, Y.-h., Ison, C., Levine, M. M., Tang, C. M. (2004). Vaccination with Attenuated Neisseria meningitidis Strains Protects against Challenge with Live Meningococci. Infect. Immun. 72: 345-351 [Abstract] [Full Text]  
  • Pasetti, M. F., Barry, E. M., Losonsky, G., Singh, M., Medina-Moreno, S. M., Polo, J. M., Ulmer, J., Robinson, H., Sztein, M. B., Levine, M. M. (2003). Attenuated Salmonella enterica Serovar Typhi and Shigella flexneri 2a Strains Mucosally Deliver DNA Vaccines Encoding Measles Virus Hemagglutinin, Inducing Specific Immune Responses and Protection in Cotton Rats. J. Virol. 77: 5209-5217 [Abstract] [Full Text]  
  • Salerno-Goncalves, R., Wyant, T. L., Pasetti, M. F., Fernandez-Vina, M., Tacket, C. O., Levine, M. M., Sztein, M. B. (2003). Concomitant Induction of CD4+ and CD8+ T Cell Responses in Volunteers Immunized with Salmonella enterica Serovar Typhi Strain CVD 908-htrA. J. Immunol. 170: 2734-2741 [Abstract] [Full Text]  
  • Jones, C. H., Dexter, P., Evans, A. K., Liu, C., Hultgren, S. J., Hruby, D. E. (2002). Escherichia coli DegP Protease Cleaves between Paired Hydrophobic Residues in a Natural Substrate: the PapA Pilin. J. Bacteriol. 184: 5762-5771 [Abstract] [Full Text]  
  • Londono-Arcila, P., Freeman, D., Kleanthous, H., O'Dowd, A. M., Lewis, S., Turner, A. K., Rees, E. L., Tibbitts, T. J., Greenwood, J., Monath, T. P., Darsley, M. J. (2002). Attenuated Salmonella enterica Serovar Typhi Expressing Urease Effectively Immunizes Mice against Helicobacter pylori Challenge as Part of a Heterologous Mucosal Priming-Parenteral Boosting Vaccination Regimen. Infect. Immun. 70: 5096-5106 [Abstract] [Full Text]  
  • Pasetti, M. F., Salerno-Goncalves, R., Sztein, M. B. (2002). Salmonella enterica Serovar Typhi Live Vector Vaccines Delivered Intranasally Elicit Regional and Systemic Specific CD8+ Major Histocompatibility Class I-Restricted Cytotoxic T Lymphocytes. Infect. Immun. 70: 4009-4018 [Abstract] [Full Text]  
  • Hindle, Z., Chatfield, S. N., Phillimore, J., Bentley, M., Johnson, J., Cosgrove, C. A., Ghaem-Maghami, M., Sexton, A., Khan, M., Brennan, F. R., Everest, P., Wu, T., Pickard, D., Holden, D. W., Dougan, G., Griffin, G. E., House, D., Santangelo, J. D., Khan, S. A., Shea, J. E., Feldman, R. G., Lewis, D. J. M. (2002). Characterization of Salmonella enterica Derivatives Harboring Defined aroC and Salmonella Pathogenicity Island 2 Type III Secretion System (ssaV) Mutations by Immunization of Healthy Volunteers. Infect. Immun. 70: 3457-3467 [Abstract] [Full Text]  
  • Dougan, G., Huett, A., Clare, S. (2002). Vaccines against human enteric bacterial pathogens. Br Med Bull 62: 113-123 [Abstract] [Full Text]  
  • Qian, F., Pan, W. (2002). Construction of a tetR-Integrated Salmonella enterica Serovar Typhi CVD908 Strain That Tightly Controls Expression of the Major Merozoite Surface Protein of Plasmodium falciparum for Applications in Human Vaccine Production. Infect. Immun. 70: 2029-2038 [Abstract] [Full Text]  
  • Bumann, D. (2001). Regulated Antigen Expression in Live Recombinant Salmonella enterica Serovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4+-T-Cell Responses. Infect. Immun. 69: 7493-7500 [Abstract] [Full Text]  
  • Jones, C. H., Bolken, T. C., Jones, K. F., Zeller, G. O., Hruby, D. E. (2001). Conserved DegP Protease in Gram-Positive Bacteria Is Essential for Thermal and Oxidative Tolerance and Full Virulence in Streptococcus pyogenes. Infect. Immun. 69: 5538-5545 [Abstract] [Full Text]  
  • Wang, J. Y., Pasetti, M. F., Noriega, F. R., Anderson, R. J., Wasserman, S. S., Galen, J. E., Sztein, M. B., Levine, M. M. (2001). Construction, Genotypic and Phenotypic Characterization, and Immunogenicity of Attenuated {Delta}guaBA Salmonella enterica Serovar Typhi Strain CVD 915. Infect. Immun. 69: 4734-4741 [Abstract] [Full Text]  
  • Turner, A. K., Terry, T. D., Sack, D. A., Londono-Arcila, P., Darsley, M. J. (2001). Construction and Characterization of Genetically Defined aro omp Mutants of Enterotoxigenic Escherichia coli and Preliminary Studies of Safety and Immunogenicity in Humans. Infect. Immun. 69: 4969-4979 [Abstract] [Full Text]  
  • Gomez-Duarte, O. G., Pasetti, M. F., Santiago, A., Sztein, M. B., Hoffman, S. L., Levine, M. M. (2001). Expression, Extracellular Secretion, and Immunogenicity of the Plasmodium falciparum Sporozoite Surface Protein 2 in Salmonella Vaccine Strains. Infect. Immun. 69: 1192-1198 [Abstract] [Full Text]  
  • Roberts, M., Chatfield, S., Pickard, D., Li, J., Bacon, A. (2000). Comparison of Abilities of Salmonella enterica Serovar Typhimurium aroA aroD and aroA htrA Mutants To Act as Live Vectors. Infect. Immun. 68: 6041-6043 [Abstract] [Full Text]  
  • Soloski, M. J., Szperka, M. E., Davies, A., Wooden, S. L. (2000). Host Immune Response to Intracellular Bacteria: A Role for MHC-Linked Class-Ib Antigen-Presenting Molecules. Exp. Biol. Med. 224: 231-239 [Abstract] [Full Text]  
  • Wang, J. Y., Noriega, F. R., Galen, J. E., Barry, E., Levine, M. M. (2000). Constitutive Expression of the Vi Polysaccharide Capsular Antigen in Attenuated Salmonella enterica Serovar Typhi Oral Vaccine Strain CVD 909. Infect. Immun. 68: 4647-4652 [Abstract] [Full Text]  
  • McSorley, S. J., Jenkins, M. K. (2000). Antibody Is Required for Protection against Virulent but Not Attenuated Salmonella enterica Serovar Typhimurium. Infect. Immun. 68: 3344-3348 [Abstract] [Full Text]  
  • Angelakopoulos, H., Hohmann, E. L. (2000). Pilot Study of phoP/phoQ-Deleted Salmonella enterica Serovar Typhimurium Expressing Helicobacter pylori Urease in Adult Volunteers. Infect. Immun. 68: 2135-2141 [Abstract] [Full Text]  
  • McNeill, H. V., Sinha, K. A., Hormaeche, C. E., Lee, J. J., Khan, C. M. A. (2000). Development of a Nonantibiotic Dominant Marker for Positively Selecting Expression Plasmids in Multivalent Salmonella Vaccines. Appl. Environ. Microbiol. 66: 1216-1219 [Abstract] [Full Text]  
  • Sydenham, M., Douce, G., Bowe, F., Ahmed, S., Chatfield, S., Dougan, G. (2000). Salmonella enterica Serovar Typhimurium surA Mutants Are Attenuated and Effective Live Oral Vaccines. Infect. Immun. 68: 1109-1115 [Abstract] [Full Text]  
  • Tacket, C. O., Sztein, M. B., Wasserman, S. S., Losonsky, G., Kotloff, K. L., Wyant, T. L., Nataro, J. P., Edelman, R., Perry, J., Bedford, P., Brown, D., Chatfield, S., Dougan, G., Levine, M. M. (2000). Phase 2 Clinical Trial of Attenuated Salmonella enterica Serovar Typhi Oral Live Vector Vaccine CVD 908-htrA in U.S. Volunteers. Infect. Immun. 68: 1196-1201 [Abstract] [Full Text]  
  • Samandari, T., Kotloff, K. L., Losonsky, G. A., Picking, W. D., Sansonetti, P. J., Levine, M. M., Sztein, M. B. (2000). Production of IFN-{gamma} and IL-10 to Shigella Invasins by Mononuclear Cells from Volunteers Orally Inoculated with a Shiga Toxin-Deleted Shigella dysenteriae Type 1 Strain. J. Immunol. 164: 2221-2232 [Abstract] [Full Text]  
  • Pickett, T. E., Pasetti, M. F., Galen, J. E., Sztein, M. B., Levine, M. M. (2000). In Vivo Characterization of the Murine Intranasal Model for Assessing the Immunogenicity of Attenuated Salmonella enterica Serovar Typhi Strains as Live Mucosal Vaccines and as Live Vectors. Infect. Immun. 68: 205-213 [Abstract] [Full Text]  
  • Galen, J. E., Nair, J., Wang, J. Y., Wasserman, S. S., Tanner, M. K., Sztein, M. B., Levine, M. M. (1999). Optimization of Plasmid Maintenance in the Attenuated Live Vector Vaccine Strain Salmonella typhi CVD 908-htrA. Infect. Immun. 67: 6424-6433 [Abstract] [Full Text]  
  • MASTROENI, P, BOWE, F, CAHILL, R, SIMMONS, C, DOUGAN, G (1999). Vaccines against gut pathogens. Gut 45: 633-635 [Full Text]  
  • Orr, N., Galen, J. E., Levine, M. M. (1999). Expression and Immunogenicity of a Mutant Diphtheria Toxin Molecule, CRM197, and Its Fragments in Salmonella typhi Vaccine Strain CVD 908-htrA. Infect. Immun. 67: 4290-4294 [Abstract] [Full Text]  
  • Ward, S. J., Douce, G., Figueiredo, D., Dougan, G., Wren, B. W. (1999). Immunogenicity of a Salmonella typhimurium aroA aroD Vaccine Expressing a Nontoxic Domain of Clostridium difficile Toxin A. Infect. Immun. 67: 2145-2152 [Abstract] [Full Text]  
  • Humphreys, S., Stevenson, A., Bacon, A., Weinhardt, A. B., Roberts, M. (1999). The Alternative Sigma Factor, sigma E, Is Critically Important for the Virulence of Salmonella typhimurium. Infect. Immun. 67: 1560-1568 [Abstract] [Full Text]  
  • Lowe, D. C., Savidge, T. C., Pickard, D., Eckmann, L., Kagnoff, M. F., Dougan, G., Chatfield, S. N. (1999). Characterization of Candidate Live Oral Salmonella typhi Vaccine Strains Harboring Defined Mutations in aroA, aroC, and htrA. Infect. Immun. 67: 700-707 [Abstract] [Full Text]  
  • Steidler, L., Robinson, K., Chamberlain, L., Schofield, K. M., Remaut, E., Le Page, R. W. F., Wells, J. M. (1998). Mucosal Delivery of Murine Interleukin-2 (IL-2) and IL-6 by Recombinant Strains of Lactococcus lactis Coexpressing Antigen and Cytokine. Infect. Immun. 66: 3183-3189 [Abstract] [Full Text]  
  • Valentine, P. J., Devore, B. P., Heffron, F. (1998). Identification of Three Highly Attenuated Salmonella typhimurium Mutants That Are More Immunogenic and Protective in Mice than a Prototypical aroA Mutant. Infect. Immun. 66: 3378-3383 [Abstract] [Full Text]  
  • Corthesy-Theulaz, I. E., Hopkins, S., Bachmann, D., Saldinger, P. F., Porta, N., Haas, R., Zheng-Xin, Y., Meyer, T., Bouzourene, H., Blum, A. L., Kraehenbuhl, J.-P. (1998). Mice Are Protected from Helicobacter pylori Infection by Nasal Immunization with Attenuated Salmonella typhimurium phoPc Expressing Urease A and B Subunits. Infect. Immun. 66: 581-586 [Abstract] [Full Text]  
  • Dunstan, S. J., Simmons, C. P., Strugnell, R. A. (1998). Comparison of the Abilities of Different Attenuated Salmonella typhimurium Strains To Elicit Humoral Immune Responses against a Heterologous Antigen. Infect. Immun. 66: 732-740 [Abstract] [Full Text]  
  • Xu, D., McSorley, S. J., Tetley, L., Chatfield, S., Dougan, G., Chan, W. L., Satoskar, A., David, J. R., Liew, F. Y. (1998). Protective Effect on Leishmania major Infection of Migration Inhibitory Factor, TNF-{alpha}, and IFN-{gamma} Administered Orally via Attenuated Salmonella typhimurium. J. Immunol. 160: 1285-1289 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»