Impact of Vector Priming on the Immunogenicity of Recombinant Salmonella Vaccines
AuthorVindurampulle, CJ; Attridge, SR
Source TitleInfection and Immunity
PublisherAmerican Society for Microbiology
University of Melbourne Author/sVINDURAMPULLE, CHRISTOFER
AffiliationMicrobiology And Immunology
Document TypeJournal Article
CitationsVindurampulle, C. J. & Attridge, S. R. (2003). Impact of Vector Priming on the Immunogenicity of Recombinant Salmonella Vaccines. Infection and Immunity, 71 (1), pp.287-297. https://doi.org/10.1128/iai.71.1.287-297.2003.
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C1 - Journal Articles Refereed
<jats:title>ABSTRACT</jats:title> <jats:p>There are conflicting reports concerning the impact of prior vector priming on the immunogenicity of recombinant-<jats:italic>Salmonella</jats:italic>-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 <jats:italic>Salmonella</jats:italic> construct. The former was investigated by constructing an <jats:italic>aroA</jats:italic> mutant of the <jats:italic>Salmonella enterica</jats:italic> serovar Stanley vector previously used in our laboratory. Although the introduction of an <jats:italic>aroA</jats:italic> 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. <jats:italic>S. enterica</jats:italic> serovar Stanley was used to deliver either of two <jats:italic>Escherichia coli</jats:italic> 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 <jats:italic>aroA S. enterica</jats:italic> 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 <jats:italic>Salmonella</jats:italic> 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 <jats:italic>Salmonella</jats:italic>-based vaccine strategy.</jats:p>
KeywordsBacteriology ; Biological Sciences
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