Induction of Host Immune Responses Using<i>Salmonella</i>‐Vectored Vaccines

Curtiss, Roy; Zhang, Xin; Wanda, Soo-Young; Kang, Ho Young; Konjufca, Vjollca; Li, Yuhua; Gunn, Bronwyn M.; Wang, Shifeng; Scarpellini, Giorgio; Lee, In Su

doi:10.1128/9781555815851.ch20

Cited by 40 publications

(82 citation statements)

References 54 publications

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“…S. Typhimurium strain 9088 was used as the vaccine strain and is described elsewhere (5,18). S. enterica expression plasmid pYA3493 (15) was used as the backbone for gene expression.…”

Section: Methodsmentioning

confidence: 99%

The Campylobacter jejuni Dps Homologue Is Important forIn VitroBiofilm Formation and Cecal Colonization of Poultry and May Serve as a Protective Antigen for Vaccination

Theoret

Cooper

Zekarias

et al. 2012

Clin Vaccine Immunol

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ABSTRACTIn this work, we investigated theCampylobacter jejuni dps(DNA binding protein from starved cells) gene for a role in biofilm formation and cecal colonization in poultry.In vitrobiofilm formation assays were conducted with stationary-phase cells in cell culture plates under microaerophilic conditions. These studies demonstrated a significant (>50%) reduction in biofilm formation by theC. jejuni dpsmutant compared to that by the wild-type strain. Studies in poultry also demonstrated the importance of thedpsgene in host colonization byC. jejuni. Real-time PCR analysis of mRNA extracted from the cecal contents of poultry infected with wild-typeC. jejuniindicated that thedpsgene is upregulated 20-fold during poultry colonization. Cecal colonization was greater than 5 log CFU lower in chicks infected with thedpsmutant than chicks infected with the wild-typeC. jejunistrain. Moreover, thedpsmutant failed to colonize 75% of the chicks following challenge with 105CFU. Preliminary studies were conducted in chicks by parenteral vaccination with a recombinant Dps protein or through oral vaccination with a recombinant attenuatedSalmonella entericastrain synthesizing theC. jejuniDps protein. No reduction inC. jejuniwas noted in chicks vaccinated with the parenteral recombinant protein, whereas, a 2.5-log-unit reduction ofC. jejuniwas achieved in chicks vaccinated with the attenuatedSalmonellavector after homologous challenge. Taken together, this work demonstrated the importance of Dps for biofilm formation and poultry colonization, and the study also provides a basis for continued work using the Dps protein as a vaccine antigen when delivered through aSalmonellavaccine vector.

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“…S. Typhimurium strain 9088 was used as the vaccine strain and is described elsewhere (5,18). S. enterica expression plasmid pYA3493 (15) was used as the backbone for gene expression.…”

Section: Methodsmentioning

confidence: 99%

The Campylobacter jejuni Dps Homologue Is Important forIn VitroBiofilm Formation and Cecal Colonization of Poultry and May Serve as a Protective Antigen for Vaccination

Theoret

Cooper

Zekarias

et al. 2012

Clin Vaccine Immunol

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“…Attenuated mutants of Salmonella enterica serovar Typhi and Salmonella enterica serovar Typhimurium have been extensively studied as multivalent vectors expressing more than 50 different bacterial, viral, and protozoan antigens in preclinical and clinical trials (14,15,19,21,58). Recombinant attenuated Salmonella vaccines (RASVs) administered orally can colonize the gut-associated lymphoid tissue (GALT) and the secondary lymphatic tissues, including the liver and spleen, and elicit mucosal, humoral, and cellular immune responses against S. enterica and heterologous antigens during infection of the mouse (14,19).…”

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confidence: 99%

“…Recombinant attenuated Salmonella vaccines (RASVs) administered orally can colonize the gut-associated lymphoid tissue (GALT) and the secondary lymphatic tissues, including the liver and spleen, and elicit mucosal, humoral, and cellular immune responses against S. enterica and heterologous antigens during infection of the mouse (14,19).…”

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confidence: 99%

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

Wei

Wanda

et al. 2008

Infect Immun

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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 ␣-helix domains of pneumococcal surface protein A (PspA) and pneumococcal surface protein C (PspC), to the signal sequences of ␤-lactamase (bla SS), ompA, and phoA and the signal sequence and C-terminal peptide of ␤-lactamase (bla SS؉CT) on Asd ؉ plasmids under the control of the P trc 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.

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“…The lethal asdA deletion is rescued by the addition of DAP to the growth medium and is needed for the antibiotic resistance-free maintenance of the runaway-like replication plasmid pYA4534, and the c2 and murA promoters were replaced with the araC P BAD activator-promoter regulatory system such that C2 and the MurA enzyme cease to be synthesized in vivo due to the lack of free arabinose. Benefits of other deletion-insertion mutations present in 9447, such as ⌬pmi-2426, ⌬(gmd-fcl)-26, ⌬P fur81 ::TTaraC, P BAD fur, ⌬P crp527 ::TT araC, P BAD crp, ⌬araE25, ⌬araBAD23, ⌬relA198::araC, and P BAD lacI TT ⌬endA2311, were described in detail previously (13,14,24,35,39,57,66).…”

Section: Resultsmentioning

confidence: 99%

Fine-Tuning Synthesis ofYersinia pestisLcrV from Runaway-Like Replication Balanced-Lethal Plasmid in aSalmonella entericaSerovar Typhimurium Vaccine Induces Protection against a LethalY. pestisChallenge in Mice

et al. 2010

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A balanced-lethal plasmid expression system that switches from low-copy-number to runaway-like highcopy-number replication (pYA4534) was constructed for the regulated delayed in vivo synthesis of heterologous antigens by vaccine strains. This is an antibiotic resistance-free maintenance system containing the asdA gene (essential for peptidoglycan synthesis) as a selectable marker to complement the lethal chromosomal ⌬asdA allele in live recombinant attenuated Salmonella vaccines (RASVs) such as Salmonella enterica serovar Typhimurium strain 9447. pYA4534 harbors two origins of replication, pSC101 and pUC (low and high copy numbers, respectively). The pUC replication origin is controlled by a genetic switch formed by the operator/ promoter of the P22 cro gene (O/P cro ) (P R ), which is negatively regulated by an arabinose-inducible P22 c2 gene located on both the plasmid and the chromosome (araC P BAD c2). The absence of arabinose, which is unavailable in vivo, triggers replication to a high-copy-number plasmid state. To validate these vector attributes, the Yersinia pestis virulence antigen LcrV was used to develop a vaccine against plague. An lcrV sequence encoding amino acids 131 to 326 (LcrV196) was optimized for expression in Salmonella, flanked with nucleotide sequences encoding the signal peptide (SS) and the carboxy-terminal domain (CT) of ␤-lactamase, and cloned into pYA4534 under the control of the P trc promoter to generate plasmid pYA4535. Our results indicate that the live Salmonella vaccine strain 9447 harboring pYA4535 efficiently stimulated a mixed Th1/Th2 immune response that protected mice against lethal challenge with Y. pestis strain CO92 introduced through either the intranasal or subcutaneous route.

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Induction of Host Immune Responses UsingSalmonella‐Vectored Vaccines

Cited by 40 publications

References 54 publications

The Campylobacter jejuni Dps Homologue Is Important forIn VitroBiofilm Formation and Cecal Colonization of Poultry and May Serve as a Protective Antigen for Vaccination

The Campylobacter jejuni Dps Homologue Is Important forIn VitroBiofilm Formation and Cecal Colonization of Poultry and May Serve as a Protective Antigen for Vaccination

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

Fine-Tuning Synthesis ofYersinia pestisLcrV from Runaway-Like Replication Balanced-Lethal Plasmid in aSalmonella entericaSerovar Typhimurium Vaccine Induces Protection against a LethalY. pestisChallenge in Mice

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