Recombinant live Salmonella spp. for human vaccination against heterologous pathogens

Bumann, Dirk; Hueck, Christoph J.; Aebischer, Toni; Meyer, Thomas

doi:10.1016/s0928-8244(99)00214-x

Cited by 29 publications

(25 citation statements)

References 61 publications

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“…Several attenuated Salmonella typhi oral vaccines have been constructed to serve as vectors for heterologous antigens, including but not limited to antigens of Shigella sonnei, Escherichia coli, Vibrio cholerae, Bordetella pertussis, Plasmodium falciparum, B. anthracis, Helicobacter pylori, and Listeria monocytogens (63)(64)(65)(66)(67)(68). As a vaccine against typhoid fever, Salmonella typhi Ty21a is a widely used licensed live vaccine that is exceedingly safe but requires three to four immunizations to induce long-term (at least 6-7 years) protective immunity in two thirds of immunized individuals (69).…”

Section: Salmonella: a Vaccine Vectormentioning

confidence: 99%

Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

2008

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Salmonella (S.) typhi is an important intracellular pathogen. Among the more than 2,300 closely-related Salmonella serovars bacteria recognized, S. typhi is the only one that is pathogenic exclusively for humans, in whom it causes typhoid or enteric fever. The pathogen has been around for many years and many studies have been done in an effort to combat it. Molecular and biologic features of S. typhi and host factors and immune responses involved in Salmonella invasion have been extensively studies. Vaccines that have been developed most notably are Vi polysaccharide and Ty21a. However, as the results show, there is still a long way to go. It is also shown that multi-drug resistance has occurred to the few available antibiotics. More and more studies have shown that Salmonella can be used as a vaccine vector carrying antigens of other pathogens. This has been promising in that the immune system can be elicited in response to both the Salmonella bacteria and the antigen of the pathogen in question. This review aims to highlight some of the milestones attained in the fight against the disease from the time S. typhi was seen as a pathogen causing typhoid fever to the use of Salmonella as a vaccine vector. Cellular & Molecular Immunology. 2008;5(2):91-97.

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Section: Salmonella: a Vaccine Vectormentioning

confidence: 99%

Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

2008

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“…This approach reveals strong differences in immunogenicity but yields no data on the minimum dose that is required to induce an efficient immune response. Adverse effects generally increase with higher vaccine doses, and this is also true for Salmonella-based vaccines (6,44,45). Hence, it is especially important to aim for Salmonella constructs that induce sufficient responses at a low inoculum size.…”

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confidence: 98%

“…strains that express foreign antigens are promising oral vaccines (6,30,41). Among the many parameters that have been shown to influence their efficacy, regulated antigen expression appears to have particularly strong effects (3,4,9,10,19,26,32,34,35,37,39,43).…”

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Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4⁺-T-Cell Responses

Bumann

2001

Infect Immun

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Regulated antigen expression can influence the immunogenicity of live recombinant Salmonella vaccines, but a rational optimization has remained difficult since important aspects of this effect are incompletely understood. Here, attenuated Salmonella enterica serovar Typhimurium SL3261 strains expressing the model antigen GFP_OVA were used to quantify in vivo antigen levels by flow cytometry and to simultaneously follow the crucial early steps of antigen-specific T-cell responses in mice that are transgenic for a T-cell receptor recognizing ovalbumin. Among seven tested promoters, P pagC has the highest activity in murine tissues combined with low in vitro expression, whereas P tac has a comparable in vivo and a very high in vitro activity. Both SL3261 (pP pagC GFP_OVA) and SL3261 (pP tac GFP_OVA) cells can induce potent ovalbumin-specific cellular immune responses following oral administration, but doses almost 1,000-fold lower are sufficient for the in vivo-inducible construct SL3261 (pP pagC GFP_OVA) compared to SL3261 (pP tac GFP_OVA). This efficacy difference is largely explained by impaired early colonization capabilities of SL3261 (pP tac GFP_OVA) cells. Based on the findings of this study, appropriate in vivo expression levels for any given antigen can be rationally selected from the increasing set of promoters with defined properties. This will allow the improvement of recombinant Salmonella vaccines against a wide range of pathogens.

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“…There have been limited investigations of the use of Ty21a as a carrier for heterologous proteins. The induction of specific antibody responses by Ty21a expressing surface-displayed viral antigens (23) or hemolysin (16) was reported in the mouse nasal model, while no humoral response but some specific T-cell responses were reported after oral vaccination of human volunteers with Ty21a expressing H. pylori urease (9,30).…”

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Salmonella enterica Serovar Typhi Ty21a Expressing Human Papillomavirus Type 16 L1 as a Potential Live Vaccine against Cervical Cancer and Typhoid Fever

Fraillery

Baud

Pang

et al. 2007

Clin Vaccine Immunol

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Human papillomavirus (HPV) vaccines based on L1 virus-like particles (VLPs) can prevent HPV-induced genital neoplasias, the precursors of cervical cancer. However, most cervical cancers occur in developing countries, where the implementation of expensive vaccines requiring multiple injections will be difficult. A live Salmonella-based vaccine could be a lower-cost alternative. We previously demonstrated that high HPV type 16 (HPV16)-neutralizing titers are induced after a single oral immunization of mice with attenuated Salmonella enterica serovar Typhimurium strains expressing a codon-optimized version of HPV16 L1 (L1S). To allow the testing of this type of vaccine in women, we constructed a new L1-expressing plasmid, kanL1S, and tested kanL1S recombinants of three Salmonella enterica serovar Typhi vaccine strains shown to be safe in humans, i.e., Ty21a, the actual licensed typhoid vaccine, and two highly immunogenic typhoid vaccine candidates, Ty800 and CVD908-htrA. In an intranasal mouse model of Salmonella serovar Typhi infection, Ty21a kanL1S was unique in inducing HPV16-neutralizing antibodies in serum and genital secretions, while anti-Salmonella responses were similar to those against the parental Ty21a vaccine. Electron microscopy examination of Ty21a kanL1S lysates showed that L1 assembled in capsomers and capsomer aggregates but not well-ordered VLPs. Comparison to the neutralizing antibody response induced by purified HPV16 L1 VLP immunizations in mice suggests that Ty21a kanL1S may be an effective prophylactic HPV vaccine. Ty21a has been widely used against typhoid fever in humans with a remarkable safety record. These finds encourage clinical testing of Ty21a kanL1S as a combined typhoid fever/cervical cancer vaccine with the potential for worldwide application.

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Recombinant live Salmonella spp. for human vaccination against heterologous pathogens

Cited by 29 publications

References 61 publications

Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4⁺-T-Cell Responses

Salmonella enterica Serovar Typhi Ty21a Expressing Human Papillomavirus Type 16 L1 as a Potential Live Vaccine against Cervical Cancer and Typhoid Fever

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Recombinant live Salmonella spp. for human vaccination against heterologous pathogens

Cited by 29 publications

References 61 publications

Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4+-T-Cell Responses

Salmonella enterica Serovar Typhi Ty21a Expressing Human Papillomavirus Type 16 L1 as a Potential Live Vaccine against Cervical Cancer and Typhoid Fever

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Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4⁺-T-Cell Responses