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Infection and Immunity, November 2008, p. 5238-5246, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00720-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A sopB Deletion Mutation Enhances the Immunogenicity and Protective Efficacy of a Heterologous Antigen Delivered by Live Attenuated Salmonella enterica Vaccines{triangledown}

Yuhua Li, Shifeng Wang, Wei Xin, Giorgio Scarpellini, Zhaoxing Shi, Bronwyn Gunn, Kenneth L. Roland, and Roy Curtiss III*

The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona 85287

Received 7 June 2008/ Returned for modification 30 July 2008/ Accepted 20 August 2008

SopB is a virulence factor of Salmonella encoded by SPI-5. Salmonella sopB deletion mutants are impaired in their ability to cause local inflammatory responses and fluid secretion into the intestinal lumen and also can enhance the immunogenicity of a vectored antigen. In this study, we evaluated the effects on immunogenicity and the efficacy of a sopB deletion mutation on two Salmonella enterica serovar Typhimurium vaccine strains with different attenuating mutations expressing a highly antigenic {alpha}-helical region of the Streptococcus pneumoniae surface protein PspA from an Asd+-balanced lethal plasmid. After oral administration to mice, the two pairs of strains induced high levels of serum antibodies specific for PspA as well as to Salmonella antigens. The levels of antigen-specific serum immunoglobulin G (IgG) and mucosal IgA were higher in mice immunized with sopB mutants. Enzyme-linked immunospot assay results indicated that the spleen cells from mice immunized with a sopB mutant showed higher interleukin-4 and gamma interferon secretion levels than did the mice immunized with the isogenic sopB+ strain. The sopB mutants also induced higher numbers of CD4+ CD44hi CD62Lhi and CD8+ CD44hi CD62Lhi central memory T cells. Eight weeks after primary oral immunization, mice were challenged with 100 50% lethal doses of virulent S. pneumoniae WU2. Immunization with either of the sopB mutant strains led to increased levels of protection compared to that with the isogenic sopB+ parent. Together, these results demonstrate that the deletion of sopB leads to an overall enhancement of the immunogenicity and efficacy of recombinant attenuated Salmonella vaccine strains.

* Corresponding author. Mailing address: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, P.O. Box 875401, 1001 S. McAllister Avenue, Tempe, AZ 85287-5401. Phone: (480) 727-0445. Fax: (480) 727-0466. E-mail: rcurtiss{at}asu.edu

{triangledown} Published ahead of print on 2 September 2008.

Editor: A. Camilli

Infection and Immunity, November 2008, p. 5238-5246, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00720-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kong, Q., Liu, Q., Roland, K. L., Curtiss, R. III (2009). Regulated Delayed Expression of rfaH in an Attenuated Salmonella enterica Serovar Typhimurium Vaccine Enhances Immunogenicity of Outer Membrane Proteins and a Heterologous Antigen. Infect. Immun. 77: 5572-5582 [Abstract] [Full Text]  
  • Xin, W., Li, Y., Mo, H., Roland, K. L., Curtiss, R. III (2009). PspA Family Fusion Proteins Delivered by Attenuated Salmonella enterica Serovar Typhimurium Extend and Enhance Protection against Streptococcus pneumoniae. Infect. Immun. 77: 4518-4528 [Abstract] [Full Text]  
  • Liu, J.-K., Hou, X.-L., Wei, C.-H., Yu, L.-Y., He, X.-J., Wang, G.-H., Lee, J.-S., Kim, C.-J. (2009). Induction of Immune Responses in Mice after Oral Immunization with Recombinant Lactobacillus casei Strains Expressing Enterotoxigenic Escherichia coli F41 Fimbrial Protein. Appl. Environ. Microbiol. 75: 4491-4497 [Abstract] [Full Text]  


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