Heterologous prime–boost immunizations with different Salmonella serovars for enhanced antigen-specific CD8 T-cell induction

Domènech, Victòria E. Sevil; Panthel, Klaus; Winter, Sebastian; Rüssmann, Holger

doi:10.1016/j.vaccine.2008.01.044

Cited by 15 publications

(14 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although heterologous priming apparently was not superior to priming with two doses of S. flexneri-based CVD 1208S (pGEN222I), our data clearly show that heterologous priming improves foreign antigen-specific humoral immune responses in mice primed using S. enterica serovar Typhi-based live vectors. A similar approach to improving cellular immunity against a foreign antigen by immunization with two different serovars of Salmonella enterica (Typhimurium and Dublin) recently was reported by Sevil Domènech et al (44). However, to our knowledge, the current work represents the first attempt to elicit an antigenspecific humoral response by presenting a common foreign antigen to the immune system using three distinct vaccination formulations (two unrelated live vector primes and a subunit protein boost).…”

Section: Discussionmentioning

confidence: 69%

Use of mchI Encoding Immunity to the Antimicrobial Peptide Microcin H47 as a Plasmid Selection Marker in Attenuated Bacterial Live Vectors

et al. 2008

View full text Add to dashboard Cite

Live attenuated bacterial strains expressing heterologous antigens represent an attractive vaccine development strategy. However, the use of drug resistance genes for the selection of expression plasmids introduced into live vectors poses theoretical health risks. Therefore, we developed a novel approach for plasmid selection based on immunity to the antimicrobial peptide microcin H47 (MccH47). Two expression plasmids encoding the reporter green fluorescent protein (GFPuv) were constructed; selection markers comprised either mchI, conferring immunity to MccH47 (pGEN222I), or bla (encoding ␤-lactamase), conferring conventional resistance to ampicillin (pGEN222). GFPuv-specific serum immunoglobulin G (IgG) antibody responses were analyzed in mice immunized intranasally either with Salmonella enterica serovar Typhi CVD 908-htrA or Shigella flexneri 2a CVD 1208S live vector and were boosted parenterally with purified GFPuv. Similar IgG antibody responses were observed for both pGEN222 and pGEN222I when either CVD 1208S or CVD 908-htrA(pGEN222I) was used as the carrier. Interestingly, CVD 908-htrA(pGEN222I) elicited a significantly higher IgG response than CVD 908-htrA(pGEN222). We also compared the priming potential of homologous priming either with CVD 908-htrA(pGEN222I) or CVD 1208S(pGEN222I) to heterologous priming first with CVD 908-htrA(pGEN222I) and then with CVD 1208S(pGEN222I) and vice versa. Immunization with two unrelated live vectors significantly enhanced the IgG responses compared to responses engendered by homologous CVD 908-htrA(pGEN222I) but not to those of CVD 1208S(pGEN222I). MccH47 offers an alternate system for plasmid selection in bacterial live vectors that greatly improves their clinical acceptability. Furthermore, the success of the heterologous priming strategy supports the feasibility of the future development of multivalent live vector-based immunization strategies against multiple human pathogens.

show abstract

Section: Discussionmentioning

confidence: 69%

Use of mchI Encoding Immunity to the Antimicrobial Peptide Microcin H47 as a Plasmid Selection Marker in Attenuated Bacterial Live Vectors

et al. 2008

View full text Add to dashboard Cite

show abstract

“…A series of experiments conducted by Sevil Domenech and colleagues demonstrated that preexisting immunity against the vector limited the induction of CD8 responses against a vectored Listeria antigen. This could be circumvented by using different Salmonella serovars for the prime and boost (25,48,49).…”

mentioning

confidence: 99%

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

View full text Add to dashboard Cite

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...

show abstract

“…In the past, the T3SS of S. enterica serovar Typhimurium became an attractive tool for heterologous protein delivery directly into the cytosol of macrophages and dendritic cells, resulting in vigorous antigen-specific CD8 T-cell priming and the induction of protective immunity against viruses, bacteria, and tumors (29,30,32,34). More recent studies from our laboratory revealed that preexisting antivector immunity can severely compromise the ability of Salmonella live vaccines to induce protective CD8 T-cell frequencies in orally immunized mice (38,39,40).…”

Section: Discussionmentioning

confidence: 99%

“…We demonstrated that the rapid clearance of the Salmonella vaccine carrier due to anti-Salmonella vector immunity after the second immunization prevents a significant elevation of T-lymphocyte numbers (38). In a more recent study, we showed that heterologous prime-boost immunizations using attenuated serovar Typhimurium and serovar Dublin strains for foreign antigen delivery can be used to bypass anti-Salmonella immunity resulting in enhanced antigen-specific CD8 T-cell induction (40). However, the translation of this heterologous prime-boost immunization approach from mice to man is not trivial due to the lack of S. enterica vaccine strains with different O antigens approved for use in humans.…”

mentioning

confidence: 89%

Superior Protective Immunity against Murine Listeriosis by Combined Vaccination with CpG DNA and RecombinantSalmonella entericaSerovar Typhimurium

et al. 2009

Self Cite

View full text Add to dashboard Cite

Preexisting antivector immunity can severely compromise the ability of Salmonella enterica serovar Typhimurium live vaccines to induce protective CD8 T-cell frequencies after type III secretion system-mediated heterologous protein translocation in orally immunized mice. To circumvent this problem, we injected CpG DNA admixed to the immunodominant p60 217-225 peptide from Listeria monocytogenes subcutaneously into BALB/c mice and coadministered a p60-translocating Salmonella strain by the orogastric route. The distribution of tetramer-positive p60 217-225 -specific effector and memory CD8 T cells was analyzed by costaining of lymphocytes with CD62L and CD127. In contrast to the single oral application of recombinant Salmonella or single immunization with CpG and p60, in the spleens from mice immunized with a combination of both vaccine types a significantly higher level of p60-specific CD8 T cells with a predominance of the effector memory T-cell subset was detected. In vivo protection studies revealed that this CD8 T-cell population conferred sterile protective immunity against a lethal infection with L. monocytogenes. However, p60-specific central memory CD8 T cells induced by single vaccination with CpG and p60 were not able confer effective protection against rapidly replicating intracellular Listeria. In conclusion, we provide compelling evidence that the combination of Salmonella type III-mediated antigen delivery and CpG immunization is an attractive novel vaccination strategy to modulate CD8 differentiation patterns toward distinct antigen-specific T-cell subsets with favorable protective capacities.The type III secretion system (T3SS) of Salmonella enterica serovar Typhimurium can be used to target heterologous antigens directly into the cytosol of antigen-presenting cells (30,32,33). Our laboratory has reported that the single oral immunization of mice with a recombinant Salmonella strain expressing the translocated Yersinia outer protein E (YopE) fused to the immunodominant antigen p60 from Listeria monocytogenes results in the efficient induction of p60-specific CD8 T cells (33). In further experiments, we explored the possibility to induce enhanced levels of antigen-specific CD8 T cells by oral boost immunization using the same recombinant serovar Typhimurium strain (38). We demonstrated that the rapid clearance of the Salmonella vaccine carrier due to anti-Salmonella vector immunity after the second immunization prevents a significant elevation of T-lymphocyte numbers (38). In a more recent study, we showed that heterologous prime-boost immunizations using attenuated serovar Typhimurium and serovar Dublin strains for foreign antigen delivery can be used to bypass anti-Salmonella immunity resulting in enhanced antigen-specific CD8 T-cell induction (40). However, the translation of this heterologous prime-boost immunization approach from mice to man is not trivial due to the lack of S. enterica vaccine strains with different O antigens approved for use in humans.An alternative vaccination strategy to ...

show abstract

Heterologous prime–boost immunizations with different Salmonella serovars for enhanced antigen-specific CD8 T-cell induction

Cited by 15 publications

References 24 publications

Use of mchI Encoding Immunity to the Antimicrobial Peptide Microcin H47 as a Plasmid Selection Marker in Attenuated Bacterial Live Vectors

Use of mchI Encoding Immunity to the Antimicrobial Peptide Microcin H47 as a Plasmid Selection Marker in Attenuated Bacterial Live Vectors

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

Superior Protective Immunity against Murine Listeriosis by Combined Vaccination with CpG DNA and RecombinantSalmonella entericaSerovar Typhimurium

Contact Info

Product

Resources

About