Mouse models for assessing the cross-protective efficacy of oral non-typhoidal Salmonella vaccine candidates harbouring in-frame deletions of the ATP-dependent protease lon and other genes.

Abstract

In BALB/c mouse models of Salmonella enterica serovar Typhimurium infection, a single oral immunization with a mutant strain with an insertion of the chloramphenicol resistance gene into the ATP-dependent protease clpP or lon gene decreased the number of salmonellae in each tissue sample 5 days after oral challenge with virulent S. Typhimurium at weeks 26 and 54 post-immunization. These data suggested that an oral immunization with the ClpP- or Lon-disrupted S. Typhimurium strain could provide long-term protection against oral challenge with virulent S. Typhimurium. Accordingly, recombinant oral non-typhoidal Salmonella (NTS) vaccines were constructed by incorporating mutants of both S. Typhimurium and S. enterica serovar Enteritidis harbouring stable in-frame markerless deletions of the clpP-lon-sulA (suppressor of lon), lon-sulA or lon-msbB (acyltransferase) genes. Amongst these orally administered vaccine candidates, those with the lon-sulA gene deletion mutants of S. Typhimurium and S. Enteritidis protected BALB/c and C57BL/6J mice against oral challenge with both virulent S. Typhimurium and virulent S. Enteritidis. Therefore, the in-frame markerless lon-sulA gene deletion mutant of S. Typhimurium or S. Enteritidis could be a promising cross-protective NTS live vaccine candidate for practical use in humans.

• Authors: Hidenori Matsui, Satoru Fukiya, Chie Kodama-Akaboshi, Masahiro Eguchi, Tomoko Yamamoto
• Journal: Journal of medical microbiology (J Med Microbiol) Vol. 64 Issue Pt 3 Pg. 295-302 (Mar 2015) ISSN: 1473-5644 [Electronic] England
• PMID: 25589672 (Publication Type: Evaluation Study, Journal Article)
• Copyright: © 2015 The Authors.

Chemical References

• Antibodies, Bacterial
• Bacterial Proteins
• DNA Primers
• Typhoid-Paratyphoid Vaccines
• Vaccines, Attenuated
• ATP-Dependent Proteases

Topics

• ATP-Dependent Proteases (genetics, immunology)
• Administration, Oral
• Animals
• Antibodies, Bacterial (immunology)
• Bacterial Proteins (genetics, immunology)
• Cross Protection
• DNA Primers (genetics)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Female
• Immunization
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Salmonella Infections, Animal (microbiology, prevention & control)
• Salmonella enteritidis (immunology)
• Salmonella typhimurium (genetics, immunology)
• Sequence Deletion
• Typhoid-Paratyphoid Vaccines (administration & dosage, immunology)
• Vaccines, Attenuated (administration & dosage, immunology)
• Virulence (genetics)