In Vivo Regulation of the Vi Antigen in Salmonella and Induction of Immune Responses with an In Vivo -Inducible Promoter
| Autor: | Victoria F. John, Robert A. Kingsley, Gordon Dougan, Carole Janis, Andrew J. Grant, Jenny Houghton, Fiona J. E. Morgan, Trevelyan J. McKinley, Pietro Mastroeni |
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| Rok vydání: | 2011 |
| Předmět: |
Salmonella
Immunology Population Enzyme-Linked Immunosorbent Assay Biology medicine.disease_cause Microbiology Mice Immune system Antigen Immunity In vivo medicine Animals Typhoid Fever Promoter Regions Genetic education Infectivity Mice Inbred BALB C education.field_of_study Attenuated vaccine Polysaccharides Bacterial Salmonella typhi Antibodies Bacterial Infectious Diseases Liver Microscopy Fluorescence Microbial Immunity and Vaccines Female Parasitology Spleen |
| Zdroj: | Infection and Immunity. 79:2481-2488 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.01265-10 |
| Popis: | Salmonella enterica serovar Typhi, the agent of typhoid fever in humans, expresses the surface Vi polysaccharide antigen that contributes to virulence. However, Vi expression can also be detrimental to some key steps of S. Typhi infectivity, for example, invasion, and Vi is the target of protective immune responses. We used a strain of S. Typhimurium carrying the whole Salmonella pathogenicity island 7 (SPI-7) to monitor in vivo Vi expression within phagocytic cells of mice at different times after systemic infection. We also tested whether it is possible to modulate Vi expression via the use of in vivo -inducible promoters and whether this would trigger anti-Vi antibodies through the use of Vi-expressing live bacteria. Our results show that Vi expression in the liver and spleen is downregulated with the progression of infection and that the Vi-negative population of bacteria becomes prevalent by day 4 postinfection. Furthermore, we showed that replacing the natural tviA promoter with the promoter of the SPI-2 gene ssaG resulted in sustained Vi expression in the tissues. Intravenous or oral infection of mice with a strain of S. Typhimurium expressing Vi under the control of the ssaG promoter triggered detectable levels of all IgG subclasses specific for Vi. Our work highlights that Vi is downregulated in vivo and provides proof of principle that it is possible to generate a live attenuated vaccine that induces Vi-specific antibodies after single oral administration. |
| Databáze: | OpenAIRE |
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