Antigen Delivery Systems II: Development of Live Recombinant Attenuated Bacterial Antigen and DNA Vaccine Delivery Vector Vaccines

Curtiss, Roy

doi:10.1016/b978-012491543-5/50060-7

Cited by 26 publications

(30 citation statements)

References 278 publications

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“…This is in contrast to the S. Typhi CVD908 Ty2 ΔaroC ΔaroD vaccine strain, which did not cause any adverse effects [72]. These results collectively imply that RpoS + S. Typhi, with or without ability to produce the Vi capsular antigen, might be superior to RpoS − strains as a vector in the development of recombinant attenuated Salmonella vaccines for humans [75,76], although they will require more effective means of attenuation that has been used previously in S. Typhi Ty2 vaccine constructions. We are currently testing this hypothesis in human volunteers.…”

Section: Vaccine Developmentmentioning

confidence: 47%

Regulation of Vi Capsular Polysaccharide Synthesis in Salmonella enterica Serotype Typhi

Santander

Roland

Curtiss

2008

J Infect Dev Ctries

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The synthesis of Vi polysaccharide, a major virulence determinant in Salmonella enterica serotype Typhi (S. Typhi), is under the control of two regulatory systems, ompR-envZ and rscB-rscC, which respond to changes in osmolarity. Some S. Typhi isolates exhibit over-expression of Vi polysaccharide, which masks clinical detection of LPS O-antigen. This variation in Vi polysaccharide and O-antigen display (VW variation) has been observed since the initial studies of S. Typhi. We have reported that the status of the rpoS gene is responsible for this phenomenon. We review the regulatory network of the Vi polysaccharide, linking osmolarity and RpoS expression. Also, we discuss how this may impact live attenuated Salmonella vaccine development.

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Section: Vaccine Developmentmentioning

confidence: 47%

Regulation of Vi Capsular Polysaccharide Synthesis in Salmonella enterica Serotype Typhi

Santander

Roland

Curtiss

2008

J Infect Dev Ctries

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“…Live attenuated Salmonella vaccines hold great potential for delivering heterologous antigens or DNAs to a variety of animal hosts to elicit protection against a number of viral, bacterial, and parasite pathogens (18,20,33,52,80). While there appears to be a need for the vaccine strain to produce high levels of antigen to elicit protection, there is a metabolic flux readjustment and redirection imposed by the diversion of the cell's resources to antigen synthesis (31,32,37,52).…”

Section: Discussionmentioning

confidence: 99%

Comparison of a Regulated Delayed Antigen Synthesis System withIn Vivo-Inducible Promoters for Antigen Delivery by Live AttenuatedSalmonellaVaccines

Wang

Shi

et al. 2011

Infect Immun

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Induction of strong immune responses against a vectored antigen in hosts immunized with live attenuated Salmonella vaccines is related in part to the amount of antigen delivered and the overall fitness of the Salmonella vector in relation to its ability to stimulate the host immune system. Constitutive high-level antigen synthesis causes a metabolic burden to the vaccine vector strain that can reduce the vaccine strain's ability to interact with host lymphoid tissues, resulting in a compromised immune response. A solution to this problem is the use of systems that regulate antigen gene expression, permitting high levels of antigen synthesis only after the vaccine strain has reached its target tissues. In vivo-inducible promoters (IVIPs) are often used to accomplish this. We recently developed an alternative strategy, a regulated delayed antigen synthesis (RDAS) system, in which the LacI-repressible P trc promoter controls antigen gene expression by adding arabinose. In this paper, we compared the RDAS system with two commonly used IVIPs, P ssaG and P pagC . Three nearly identical plasmids, differing only in the promoter used to direct transcription of the pneumococcal pspA gene, P trc , P ssaG , or P pagC , were constructed and introduced into isogenic Salmonella vaccine strains with or without arabinose-inducible LacI synthesis. Mice immunized with the RDAS strain developed slightly higher titers of mucosal and serum anti-PspA antibodies than P pagC -immunized mice, while titers in mice immunized with the P ssaG strain were 100-fold lower. Both the RDAS and P pagC strains conferred similar levels of protection against Streptococcus pneumoniae challenge, significantly greater than those for the P ssaG strain or controls. Thus, RDAS provides another choice for inclusion in the live vaccine design to increase immunogenicity.

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“…A number of factors may affect the immune response to protective antigens, including the abilities of vaccine strains to invade and colonize the host GALT, the stability of the plasmid expression system, and the antigen subcellular location (14,19,38). High-level expression of protective antigens by RASV strains often imposes an energy demand that decreases growth, fitness, and the ability to colonize lymphoid tissues, resulting in further attenuation and a reduction in immunogenicity (7,14,51).…”

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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%

“…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%

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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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Antigen Delivery Systems II: Development of Live Recombinant Attenuated Bacterial Antigen and DNA Vaccine Delivery Vector Vaccines

Cited by 26 publications

References 278 publications

Regulation of Vi Capsular Polysaccharide Synthesis in Salmonella enterica Serotype Typhi

Regulation of Vi Capsular Polysaccharide Synthesis in Salmonella enterica Serotype Typhi

Comparison of a Regulated Delayed Antigen Synthesis System withIn Vivo-Inducible Promoters for Antigen Delivery by Live AttenuatedSalmonellaVaccines

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

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