Vector Priming Reduces the Immunogenicity ofSalmonella-Based Vaccines inNramp1+/+Mice

Vindurampulle, Christofer J.; Attridge, Stephen R.

doi:10.1128/iai.71.4.2258-2261.2003

Cited by 9 publications

(7 citation statements)

References 19 publications

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“…Similar results were obtained in a later study (46,59), which reported that prior exposure of animals to homologous or related strains reduced the subsequent immune response in mice against the vectored foreign antigen. Finally, Attridge and Vindurampulle found that the hyporesponsiveness could be largely eliminated by exposing animals to the foreign antigen prior to vector priming (7).…”

supporting

confidence: 89%

Influence of Promoter, Gene Copy Number, and Preexisting Immunity on Humoral and Cellular Responses to a Vectored Antigen Delivered by a Salmonella enterica Vaccine

Saxena

Coloe

Smooker

2009

Clin Vaccine Immunol

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Attenuated Salmonella strains are currently in production as vaccines for protection of animals against salmonellosis. Such commercial strains offer the potential to deliver heterologous antigen to protect animals against other diseases. One vaccine strain, attenuated Salmonella enterica serovar Typhimurium (STM-1), was tested for the ability to deliver ovalbumin and to induce immune responses in mice. Two vaccine trials were performed testing the influence of promoter choice, the location of the encoding DNA (plasmid or chromosome), and the effect of preexisting homologous or heterologous immunity. The results demonstrated that humoral and T-cell responses were induced from either of two promoters, from either the plasmid or the chromosome, and that preexposure to the empty homologous vector, STM-1, or the heterologous vector, S. enterica serovar Enteritidis, had no detrimental effect on subsequent antigen-specific responses. In the case of homologous preexposure, responses were generally greater, and this was correlated with an increased uptake of Salmonella by macrophages in vitro after opsonization with immune sera.Salmonella enterica strains have been well characterized for the delivery of heterologous vaccine antigens in several animal models (4,5,8, 11, 22,39,43,50). The potential advantages of live attenuated vaccines, such as the simple mode of inoculation and generation of strong immune responses, make them ideal candidates for the delivery of antigens (38-40, 57). Infection by Salmonella induces both humoral and cell-mediated responses, not only against homologous antigens, but also against the heterologous antigen for which they act as a carrier (2, 16, 32,36,41,43).STM-1 is an S. enterica serovar Typhimurium mutant developed by RMIT and harbors a mutation in the aroA gene region that renders it attenuated (M. Saxena, P. Smooker, and P. Coloe, submitted for publication). It is a commercial vaccine strain currently in use to protect livestock against Salmonella infection (1). It is delivered to the immune system of chickens by spraying or administration via drinking water and therefore enters via mucosal tissues. It has been previously demonstrated that STM-1 is capable of eliciting immune responses in mice to model plasmid-borne antigens (8) and from inserts integrated at a chromosomal location (55). We have extended these studies to further analyze the capacity of STM-1 in three ways: first, a comparison between plasmid-and chromosome-borne delivery routes using two different promoters; second, an analysis of the T-cell responses induced in mice, in addition to humoral responses; and last, an experiment designed to investigate the influence of preexisting immunity to the vaccine vector. Emphasis was given to an analysis of expression from the chromosomal location, since in order to progress to any commercial application, the use of plasmid-borne antigens should be eliminated. There are two main reasons for this: (i) to ensure the stability of antigen expression in the absence of plasmid selection an...

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supporting

confidence: 89%

Influence of Promoter, Gene Copy Number, and Preexisting Immunity on Humoral and Cellular Responses to a Vectored Antigen Delivered by a Salmonella enterica Vaccine

Saxena

Coloe

Smooker

2009

Clin Vaccine Immunol

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“…The various reports are contradictory in their findings and seem to paint a rather confusing picture. Some studies concluded that pre-existing immunity against the Salmonella vector leads to stronger immune responses against the delivered antigen (Bao & Clements, 1991; Jespersgaard et al , 2001; Kohler et al , 2000a, b; Metzger et al , 2004; Saxena et al , 2009; Sevil Domènech et al , 2008; Whittle & Verma, 1997), with others considering pre-existing immunity to be a limiting factor in the long-term use of Salmonella as an efficient vector for antigen delivery (Attridge et al , 1997; Gahan et al , 2008; Roberts et al , 1999; Sevil Domènech et al , 2007; Vindurampulle & Attridge, 2003a, b). …”

Section: Effects Of Prior Immunological Exposure To Vectors – Bacterimentioning

confidence: 99%

Pre-existing immunity against vaccine vectors – friend or foe?

et al. 2013

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Over the last century, the successful attenuation of multiple bacterial and viral pathogens has led to an effective, robust and safe form of vaccination. Recently, these vaccines have been evaluated as delivery vectors for heterologous antigens, as a means of simultaneous vaccination against two pathogens. The general consensus from published studies is that these vaccine vectors have the potential to be both safe and efficacious. However, some of the commonly employed vectors, for example Salmonella and adenovirus, often have pre-existing immune responses in the host and this has the potential to modify the subsequent immune response to a vectored antigen. This review examines the literature on this topic, and concludes that for bacterial vectors there can in fact, in some cases, be an enhancement in immunogenicity, typically humoral, while for viral vectors pre-existing immunity is a hindrance for subsequent induction of cell-mediated responses.

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“…However, it is important to mention that one of the disadvantages of using Salmonella as a vector for expression of heterologous antigens is the fact that previous exposure to Salmonella can significantly reduce the induction of immunity against heterologous antigens after a second challenge [145,[148][149][150]. This phenomenon is probably due to the rapid clearance of the vector by components of the adaptive immune response after a secondary infection, resulting in a reduction of the amount of heterologous antigen available for APCs [151].…”

Section: Modulation Of Immune Response By Expression Level and Cellulmentioning

confidence: 99%

“…In the case of EAE, immunization with Salmonella-CFA/I previous to EAE induction prevented demyelination and infiltration of inflammatory cells in the central nervous system. As a result, previous exposure to the recombinant Salmonella strain led to a significant reduction in the clinical score caused by challenge with the autoantigen-derived PLP (139)(140)(141)(142)(143)(144)(145)(146)(147)(148)(149)(150)(151) peptide [182,183]. There is evidence suggesting that expansion of regulatory, FoxP3 positive T cells (Treg) is required for the induction of tolerance caused by immunization with CFA/I recombinant Salmonella, independently of autoantigen challenge [182].…”

Section: Use Of Salmonella To Induce Tolerance To Self-antigensmentioning

confidence: 99%

Use of Genetically Modified Bacteria to Modulate Adaptive Immunity

Bueno

González²,

Kalergis³

2009

CGT

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Infectious diseases caused by virulent bacteria are a significant cause of morbidity and mortality worldwide, especially in developing countries. However, attenuated strains derived from pathogenic bacteria, such as Salmonella, are highly immunogenic and can be used as vaccines to promote immunity against parental pathogenic bacteria strains. Further, they can be genetically manipulated to either express foreign antigens or deliver exogenous DNA, in order to induce immunity against other pathogens or antigens. Contrarily, specific structural modifications in attenuated Salmonella have allowed the generation of strains that can be well tolerated by the immune system and reduce inflammatory responses. It is thought that those strains could be considered as vectors to promote specific immune tolerance for certain auto-antigens or allergens and reduce unwanted or self-reactive immune responses. In addition, some structural features of Salmonella can contribute to defining the nature and type of polarization of the adaptive immune response induced after immunization, which can be considered as a tool to modulate antigen-specific immunity. In this article we discuss recent advances in the understanding of immune system modulation by molecular components of bacteria and their exploitation for the rational induction of pathogen immunity or antigen-specific tolerance.

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Vector Priming Reduces the Immunogenicity ofSalmonella-Based Vaccines inNramp1^+/+Mice

Cited by 9 publications

References 19 publications

Influence of Promoter, Gene Copy Number, and Preexisting Immunity on Humoral and Cellular Responses to a Vectored Antigen Delivered by a Salmonella enterica Vaccine

Influence of Promoter, Gene Copy Number, and Preexisting Immunity on Humoral and Cellular Responses to a Vectored Antigen Delivered by a Salmonella enterica Vaccine

Pre-existing immunity against vaccine vectors – friend or foe?

Use of Genetically Modified Bacteria to Modulate Adaptive Immunity

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