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Infection and Immunity, July 2008, p. 3241-3254, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.01623-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Analysis of Type II Secretion of Recombinant Pneumococcal PspA and PspC in a Salmonella enterica Serovar Typhimurium Vaccine with Regulated Delayed Antigen Synthesis{triangledown}

Wei Xin, Soo-Young Wanda, Yuhua Li, Shifeng Wang, Hua Mo, and Roy Curtiss III*

Center for Infectious Diseases and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287

Received 6 December 2007/ Returned for modification 9 January 2008/ Accepted 28 April 2008

Recombinant attenuated Salmonella vaccines (RASVs) have been used extensively to express and deliver heterologous antigens to host mucosal tissues. Immune responses can be enhanced greatly when the antigen is secreted to the periplasm or extracellular compartment. The most common method for accomplishing this is by fusion of the antigen to a secretion signal sequence. Finding an optimal signal sequence is typically done empirically. To facilitate this process, we constructed a series of plasmid expression vectors, each containing a different type II signal sequence. We evaluated the utilities of these vectors by fusing two different antigens, the {alpha}-helix domains of pneumococcal surface protein A (PspA) and pneumococcal surface protein C (PspC), to the signal sequences of β-lactamase (bla SS), ompA, and phoA and the signal sequence and C-terminal peptide of β-lactamase (bla SS+CT) on Asd+ plasmids under the control of the Ptrc promoter. Strains were characterized for level of expression, subcellular antigen location, and the capacity to elicit antigen-specific immune responses and protection against challenge with Streptococcus pneumoniae in mice. The immune responses to each protein differed depending on the signal sequence used. Strains carrying the bla SS-pspA and bla SS+CT-pspC fusions yielded the largest amounts of secreted PspA and PspC, respectively, and induced the highest serum IgG titers, although all fusion proteins tested induced some level of antigen-specific IgG response. Consistent with the serum antibody responses, RASVs expressing the bla SS-pspA and bla SS+CT-pspC fusions induced the greatest protection against S. pneumoniae challenge.

* Corresponding author. Mailing address: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, 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 5 May 2008.

Editor: F. C. Fang

Infection and Immunity, July 2008, p. 3241-3254, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.01623-07
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]  
  • Ko, H.-J., Yang, J.-Y., Shim, D.-H., Yang, H., Park, S.-M., Curtiss, R. III, Kweon, M.-N. (2009). Innate Immunity Mediated by MyD88 Signal Is Not Essential for Induction of Lipopolysaccharide-Specific B Cell Responses but Is Indispensable for Protection against Salmonella enterica serovar Typhimurium infection. J. Immunol. 182: 2305-2312 [Abstract] [Full Text]  
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