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

 Previous Article  |  Next Article 

Infection and Immunity, July 2002, p. 3457-3467, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3457-3467.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Characterization of Salmonella enterica Derivatives Harboring Defined aroC and Salmonella Pathogenicity Island 2 Type III Secretion System (ssaV) Mutations by Immunization of Healthy Volunteers

Microscience, Wokingham Berkshire RG41 5TU,¹ Departments of Infectious Diseases,² Microbiology, St. George's Hospital Medical School, London SW17 0RE,³ Centre for Molecular Microbiology and Infection, Imperial College of Science, Technology, and Medicine, London SW7 2AZ, United Kingdom⁴

Received 26 November 2001/ Returned for modification 8 January 2002/ Accepted 11 March 2002

The attenuation and immunogenicity of two novel Salmonella vaccine strains, Salmonella enterica serovar Typhi (Ty2 aroC ssaV, designated ZH9) and S. enterica serovar Typhimurium (TML aroC ssaV, designated WT05), were evaluated after their oral administration to volunteers as single escalating doses of 10⁷, 10⁸, or 10⁹ CFU. ZH9 was well tolerated, not detected in blood, nor persistently excreted in stool. Six of nine volunteers elicited anti-serovar Typhi lipopolysaccharide (LPS) immunoglobulin A (IgA) antibody-secreting cell (ASC) responses, with three of three vaccinees receiving 10⁸ and two of three receiving 10⁹ CFU which elicited high-titer LPS-specific serum IgG. WT05 was also well tolerated with no diarrhea, although the administration of 10⁸ and 10⁹ CFU resulted in shedding in stools for up to 23 days. Only volunteers immunized with 10⁹ CFU of WT05 mounted detectable serovar Typhimurium LPS-specific ASC responses and serum antibody responses were variable. These data indicate that mutations in type III secretion systems may provide a route to the development of live vaccines in humans and highlight significant differences in the potential use of serovars Typhimurium and Typhi.

Editor: D. L. Burns

This article has been cited by other articles:

• Echchannaoui, H., Bianchi, M., Baud, D., Bobst, M., Stehle, J.-C., Nardelli-Haefliger, D. (2008). Intravaginal Immunization of Mice with Recombinant Salmonella enterica Serovar Typhimurium Expressing Human Papillomavirus Type 16 Antigens as a Potential Route of Vaccination against Cervical Cancer. Infect. Immun. 76: 1940-1951 [Abstract] [Full Text]  
• Coburn, B., Sekirov, I., Finlay, B. B. (2007). Type III Secretion Systems and Disease. Clin. Microbiol. Rev. 20: 535-549 [Abstract] [Full Text]  
• Abd El Ghany, M., Jansen, A., Clare, S., Hall, L., Pickard, D., Kingsley, R. A., Dougan, G. (2007). Candidate Live, Attenuated Salmonella enterica Serotype Typhimurium Vaccines with Reduced Fecal Shedding Are Immunogenic and Effective Oral Vaccines. Infect. Immun. 75: 1835-1842 [Abstract] [Full Text]  
• Santander, J., Wanda, S.-Y., Nickerson, C. A., Curtiss, R. III (2007). Role of RpoS in Fine-Tuning the Synthesis of Vi Capsular Polysaccharide in Salmonella enterica Serotype Typhi. Infect. Immun. 75: 1382-1392 [Abstract] [Full Text]  
• Ku, Y.-W., McDonough, S. P., Palaniappan, R. U. M., Chang, C.-F., Chang, Y.-F. (2005). Novel Attenuated Salmonella enterica Serovar Choleraesuis Strains as Live Vaccine Candidates Generated by Signature-Tagged Mutagenesis. Infect. Immun. 73: 8194-8203 [Abstract] [Full Text]  
• Kirkpatrick, B. D., Bentley, M. D., Thern, A. M., Larsson, C. J., Ventrone, C., Sreenivasan, M. V., Bourgeois, L. (2005). Comparison of the Antibodies in Lymphocyte Supernatant and Antibody-Secreting Cell Assays for Measuring Intestinal Mucosal Immune Response to a Novel Oral Typhoid Vaccine (M01ZH09). CVI 12: 1127-1129 [Abstract] [Full Text]  
• Stratford, R., McKelvie, N. D., Hughes, N. J., Aldred, E., Wiseman, C., Curtis, J., Bellaby, T., Bentley, M., Hindle, Z., Brennan, F. R., Chatfield, S. N., Dougan, G., Khan, S. A. (2005). Optimization of Salmonella enterica Serovar Typhi {Delta}aroC {Delta}ssaV Derivatives as Vehicles for Delivering Heterologous Antigens by Chromosomal Integration and In Vivo Inducible Promoters. Infect. Immun. 73: 362-368 [Abstract] [Full Text]  
• Lyons, S., Wang, L., Casanova, J. E., Sitaraman, S. V., Merlin, D., Gewirtz, A. T. (2004). Salmonella typhimurium transcytoses flagellin via an SPI2-mediated vesicular transport pathway. J. Cell Sci. 117: 5771-5780 [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]  
• Haque, A, Bowe, F, Fitzhenry, R J, Frankel, G, Thomson, M, Heuschkel, R, Murch, S, Stevens, M P, Wallis, T S, Phillips, A D, Dougan, G (2004). Early interactions of Salmonella enterica serovar typhimurium with human small intestinal epithelial explants. Gut 53: 1424-1430 [Abstract] [Full Text]  
• Schmidt, H., Hensel, M. (2004). Pathogenicity Islands in Bacterial Pathogenesis. Clin. Microbiol. Rev. 17: 14-56 [Abstract] [Full Text]  
• Kingsley, R. A., Humphries, A. D., Weening, E. H., de Zoete, M. R., Winter, S., Papaconstantinopoulou, A., Dougan, G., Baumler, A. J. (2003). Molecular and Phenotypic Analysis of the CS54 Island of Salmonella enterica Serotype Typhimurium: Identification of Intestinal Colonization and Persistence Determinants. Infect. Immun. 71: 629-640 [Abstract] [Full Text]