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Infection and Immunity, January 2003, p. 287-297, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.287-297.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Impact of Vector Priming on the Immunogenicity of Recombinant Salmonella Vaccines

Christofer J. Vindurampulle{dagger} and Stephen R. Attridge*

Department of Molecular Biosciences, The University of Adelaide, Adelaide, South Australia 5005, Australia

Received 29 July 2002/ Returned for modification 12 September 2002/ Accepted 22 October 2002

There are conflicting reports concerning the impact of prior vector priming on the immunogenicity of recombinant-Salmonella-based vaccines. A comparison of experimental protocols identified two variables which might account for this inconsistency: the potential of the vector strain to colonize the murine gut-associated lymphoid tissue (GALT) and the nature of the foreign antigen subsequently delivered by the recombinant Salmonella construct. The former was investigated by constructing an aroA mutant of the Salmonella enterica serovar Stanley vector previously used in our laboratory. Although the introduction of an aroA mutation had surprisingly little effect on GALT colonization, it did reduce the strength of antilipopolysaccharide (anti-LPS) antibody responses and the impact of vector priming. Studies were also performed to ascertain the extent to which any observed hyporesponsiveness consequent upon vector priming might be determined by the characteristics of the foreign antigen. S. enterica serovar Stanley was used to deliver either of two Escherichia coli antigens, K88 pilus protein or the LT-B toxin subunit, to vector-primed mice. Both serum immunoglobulin G (IgG) and intestinal IgA responses to K88 were completely abolished, and those to LT-B were significantly reduced, as a consequence of vector priming. When similar experiments were performed with an aroA S. enterica serovar Dublin vector, responses to K88 were significantly reduced but those to LT-B were unaffected by vector priming. Paradoxically, a priming infection with this vector induced stronger anti-LPS antibody responses but was less likely to elicit a state of hyporesponsiveness to subsequently presented foreign antigen. The impact of vector priming thus depends on both the Salmonella strain used and the nature of the foreign antigen, but our present data strengthen concerns that preexisting antivector immunity represents a serious threat to the Salmonella-based vaccine strategy.

* Corresponding author. Mailing address: Department of Molecular Biosciences, The University of Adelaide, Adelaide, South Australia 5005, Australia. Phone: 61-8-83034150. Fax: 61-8-83037532. E-mail: stephen.attridge{at}adelaide.edu.au.

Editor: J. D. Clements

{dagger} Present address: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Md.

Infection and Immunity, January 2003, p. 287-297, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.287-297.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Saxena, M., Coloe, P. J., Smooker, P. M. (2009). Influence of Promoter, Gene Copy Number, and Preexisting Immunity on Humoral and Cellular Responses to a Vectored Antigen Delivered by a Salmonella enterica Vaccine. CVI 16: 78-87 [Abstract] [Full Text]  
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  • Vindurampulle, C. J., Attridge, S. R. (2003). Vector Priming Reduces the Immunogenicity of Salmonella-Based Vaccines in Nramp1+/+ Mice. Infect. Immun. 71: 2258-2261 [Abstract] [Full Text]  


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