Comparison of a fimbrial versus an autotransporter display system for viral epitopes on an attenuated Salmonella vaccine vector

Chen, Huaiqing; Schifferli, Dieter M.

doi:10.1016/j.vaccine.2006.11.006

Cited by 18 publications

(13 citation statements)

References 38 publications

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“…Previous addition of the spiC promoter, which is activated in antigen-presenting cells, was used successfully to express the MisL protein or the 987P fimbriae of E. coli as viral epitope carriers on the surface of a Salmonella vaccine vector. Oral immunization experiments in mice also suggested improved in vivo expression by showing better humoral immune responses against the foreign antigens [ 10 , 24 ]. Thus, we prepared a similar promoter tandem construct by inserting the spiC promoter between the nirB promoter and the Shine Delgarno site for MisL transcription (Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…A recent study suggested that location on the bacterial surface was even more important for immunity than high abundance or immunodominance since Salmonella mainly survive in antigen-presenting cells, rendering surface antigens more accessible to the cell for processing and presentation [ 30 ]. Second, surface-exposed foreign epitopes presented as multimers induced better antibody responses than the same epitopes presented as monomers on a Salmonella vaccine vector [ 10 ]. Because it is capable of expressing antigens on a Salmonella surface, the MisL protein has the advantage of tolerating large fragments of proteins in a fusion construct.…”

Section: Discussionmentioning

confidence: 99%

“…The epitopes were shown to induce immune responses. Similarly, viral and parasitic protein epitopes were successfully expressed by recombinant MisL on Salmonella vaccine strains and induced epitope-specific immune responses with protective properties [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface display on Salmonella

et al. 2014

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BackgroundAutotransporter proteins represent a treasure trove for molecular engineers who modify Gram-negative bacteria for the export or secretion of foreign proteins across two membrane barriers. A particularly promising direction is the development of autotransporters as antigen display or secretion systems. Immunologists have been using ovalbumin as a reporter antigen for years and have developed sophisticated tools to detect specific T cells that respond to ovalbumin. Although ovalbumin-expressing bacteria are being used to trace T cell responses to colonizing or invading pathogens, current constructs for ovalbumin presentation have not been optimized.ResultsThe activation of T helper cells in response to ovalbumin was improved by displaying the OVA-CD4 reporter epitope as a multimer on the surface of Salmonella and fused to the autotransporter MisL. Expression was optimized by including tandem in vivo promoters and two post-segregational killing systems for plasmid stabilization.ConclusionsThe use of an autotransporter protein to present relevant epitope repeats on the surface of bacteria, combined with additional techniques favoring stable and efficient in vivo transcription, optimizes antigen presentation to T cells. The technique of multimeric epitope surface display should also benefit the development of new Salmonella or other enterobacterial vaccines.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface display on Salmonella

et al. 2014

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“…Surface-exposed foreign epitopes are often presented as multimers and could induce better immune responses than the same epitopes presented as monomers in a Salmonella vaccine (31). Therefore, antigen expressed on Salmonella surface using surface display system can induce better CD4 þ T response.…”

Section: Discussionmentioning

confidence: 99%

Combining DNA Vaccine and AIDA-1 in AttenuatedSalmonellaActivates Tumor-Specific CD4+ and CD8+ T-cell Responses

Zhao

Liu

et al. 2017

Cancer Immunology Research

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Stimulation of tumor-specific responses in both CD4 þ and CD8 þ T cells has been a challenge for effective tumor vaccines. We designed a vaccine vector containing the AIDA-1 autotransporter and DNA vaccine elements, generating a murine melanoma vaccine that was delivered by the attenuated Salmonella strain SL7207. Growth of murine subcutaneous melanoma was significantly inhibited by intranasal immunization with the Salmonella tumor vaccine. The vaccine activated tumor-specific CD4 þ and CD8 þ T-cell responses, with increased T-cell proliferation, tumor antigen-specific Th1 cytokine production, increased percentages of tetramer positive cells, and cytotoxicity. CD4 þ or CD8 þ T-cell depletion resulted in the loss of antitumor activity of the Salmonella tumor vaccine, suggesting that the efficacy of the vaccine was dependent on both CD4 þ and CD8 þ T cells. Lung metastasis of the tumor was also inhibited by vaccine treatment. Similarly, the percentages of tumor-specific Th1 cytokine production by CD4 þ and CD8 þ T cells in the spleen, tumor, and bronchoalveolar lavage were increased after vaccine treatment. Tumor-specific proliferation of CD4 þ and CD8 þ T cells was also promoted by the vaccine. Tetramer staining and cytotoxicity assay showed enhanced tumor-specific CD8 þ T-cell response after vaccine treatment. Therefore, the Salmonella tumor vaccine could activate both tumor-specific CD4 þ and CD8 þ T-cell responses. This vaccine strategy may be widely applicable to the development of oral or nasal vaccines against tumors.

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“…Although autodisplay has become a system of choice for recombinant protein expression for various applications, there are limited studies comparing the effects of secreted versus cell surface-bound antigen on host immune responses ( 33 ). Nevertheless, some studies have suggested that protrusion of the target antigen away from bacterial cell surface structures may facilitate protective immunity ( 34 ). This implies that the mode of antigen presentation to the immune system, rather than intrinsic properties of the antigen and/or expression levels, can determine immunogenicity.…”

Section: Introductionmentioning

confidence: 99%

Antigen Localization Influences the Magnitude and Kinetics of Endogenous Adaptive Immune Response to Recombinant Salmonella Vaccines

et al. 2017

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The use of recombinant attenuated Salmonella vaccine (RASV) strains is a promising strategy for presenting heterologous antigens to the mammalian immune system to induce both cellular and humoral immune responses. However, studies on RASV development differ on where heterologous antigens are expressed and localized within the bacterium, and it is unclear how antigen localization modulates the immune response. Previously, we exploited the plasmid-encoded toxin (Pet) autotransporter system for accumulation of heterologous antigens in cell culture supernatant. In the present study, this Pet system was used to express early secretory antigen 6 (ESAT-6), an immunodominant and diagnostic antigen from Mycobacterium tuberculosis, in Salmonella enterica serovar Typhimurium strain SL3261. Three strains were generated, whereby ESAT-6 was expressed as a cytoplasmic (SL3261/cyto), surface-bound (SL3261/surf), or secreted (SL3261/sec) antigen. Using these RASVs, the relationship between antigen localization and immunogenicity in infected C57BL/6 mice was systematically examined. Using purified antigen and specific tetramers, we showed that mice infected with the SL3261/surf or SL3261/sec strain generated large numbers of Th1 CD4+ ESAT-6+ splenic T cells compared to those of mice infected with SL3261/cyto. While all mice showed ESAT-6-specific antibody responses when infected with SL3261/surf or SL3261/sec, peak total serum IgG antibody titers were reached more rapidly in mice that received SL3261/sec. Thus, how antigen is localized after production within bacteria has a more marked effect on the antibody response than on the CD4+ T cell response, which might influence the chosen strategy to localize recombinant antigen in RASVs.

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Comparison of a fimbrial versus an autotransporter display system for viral epitopes on an attenuated Salmonella vaccine vector

Cited by 18 publications

References 38 publications

Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface display on Salmonella

Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface display on Salmonella

Combining DNA Vaccine and AIDA-1 in AttenuatedSalmonellaActivates Tumor-Specific CD4+ and CD8+ T-cell Responses

Antigen Localization Influences the Magnitude and Kinetics of Endogenous Adaptive Immune Response to Recombinant Salmonella Vaccines

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