Oral immunization with a shiga toxin B subunit::rotavirus NSP490 fusion protein protects mice against gastroenteritis

Choi, Nak-Won; Estes, Mary K.; Langridge, William H. R.

doi:10.1016/j.vaccine.2005.06.015

Cited by 23 publications

(19 citation statements)

References 27 publications

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“…A similar finding seems to be true for NSP4 and RV-induced disease. Immunization of mice with either the enterotoxic peptide (aa114-135) or the entire NSP4 C-terminus (aa85-175) linked to either the cholera toxin or shiga toxin B subunit, which serves as an adjuvant, stimulates both systemic (IgG) and mucosal (IgA) antibody responses [51;52]. Pups born to NSP4-vaccinated dams exhibit significantly reduced severity and duration of diarrhea compared to pups born to unvaccinated dams [51;52].…”

Section: Nsp4: a Future Therapeutic Targetmentioning

confidence: 99%

“…Immunization of mice with either the enterotoxic peptide (aa114-135) or the entire NSP4 C-terminus (aa85-175) linked to either the cholera toxin or shiga toxin B subunit, which serves as an adjuvant, stimulates both systemic (IgG) and mucosal (IgA) antibody responses [51;52]. Pups born to NSP4-vaccinated dams exhibit significantly reduced severity and duration of diarrhea compared to pups born to unvaccinated dams [51;52]. Although these studies did not determine which epitope(s) on NSP4 stimulated the protective antibody, earlier studies found immunization with the aa114-135 peptide generates an antibody response that protects against diarrhea [21] and this protective antibody is specific to a single NSP4 epitope that is 100% conserved in all NSP4 sequences [48;53].…”

Section: Nsp4: a Future Therapeutic Targetmentioning

confidence: 99%

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Rotavirus vaccines and pathogenesis: 2008

Hyser

Estes

2009

Current Opinion in Gastroenterology

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Purpose of Review-Rotaviruses cause life-threatening gastroenteritis in children throughout the world. The burden of disease has resulted in the development of two live, attenuated vaccines that are now licensed in many countries. This review summarizes new data on these vaccines, their effectiveness, and remaining challenges including new data on the rotavirus enterotoxin, a potential antiviral target.Recent findings-Live attenuated rotavirus vaccines are used to protect infants against severe rotavirus-induced gastroenteritis and, RotaTeq®, a pentavalent bovine based vaccine, and, Rotarix®, a monovalent human rotavirus, are now currently licensed in many countries. Initial results of the licensed RotaTeq® vaccine have been promising in the United States and results of immunogenicity and efficacy in developing countries are expected soon. However universal vaccine implementation is challenging due to age limitations on administration of these vaccines. Chronic rotavirus infections in immunocompromised children may remain a problem and require the development of new treatments including antiviral drugs. Increasing data on the mechanisms of action of the rotavirus enterotoxin highlight this pleiotropic protein as a good target as well as unique calcium agonist.Summary-Rotavirus is now a commonly occurring vaccine-preventable disease among children in developed countries and hopefully this also will soon be true for developing countries. Future studies will determine if other methods of prevention, such as nonreplicating vaccines and antiviral drugs, will be needed to treat disease in immunocompromised children.

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Section: Nsp4: a Future Therapeutic Targetmentioning

confidence: 99%

Section: Nsp4: a Future Therapeutic Targetmentioning

confidence: 99%

Rotavirus vaccines and pathogenesis: 2008

Hyser

Estes

2009

Current Opinion in Gastroenterology

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“…Gb 3 is almost exclusively expressed on APC such as DC and B cells among hematopoietic cells [23]. Recently, it was shown that oral immunization with STxB linked to a fragment of the immunogenic rotavirus nonstructural protein (NSP4) protects mice against gastroenteritis mediated by a rotavirus challenge, and this was associated with a strong Th1-mediated response [24]. In a previous study, we showed that STxB efficiently targets exogenous peptides into the MHC class I pathway and induces humoral and cell-mediated immune responses [25].…”

Section: Introductionmentioning

confidence: 99%

The Shiga toxin B‐subunit targets antigen in vivo to dendritic cells and elicits anti‐tumor immunity

et al. 2006

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The non-toxic B-subunit of Shiga toxin (STxB) interacts with the glycolipid Gb 3 , which is preferentially expressed on dendritic cells (DC) and B cells. After administration of STxB chemically coupled to OVA (STxB-OVA) in mice, we showed that the immunodominant OVA 257-264 peptide restricted by K b molecules is specifically presented by CD11c + CD8a -DC, some of them displaying a mature phenotype. Using mice carrying a transgene encoding a diphtheria toxin receptor (DTR) under the control of the murine CD11c promoter, which allows inducible ablation of DC, we showed that DC are required for efficient priming of CTL after STxB-OVA vaccination. Immunization of mice with STxB-OVA induced OVA-specific CD8 + T cells detected ex vivo; these cells were long lasting, since they could be detected even 91 days after the last immunization and were composed of both central and memory T cells. Vaccination of mice with STxB-OVA and STxB coupled to E7, a protein derived from HPV16, inhibited tumor growth in prophylactic and therapeutic experiments. This effect was mainly mediated by CD8 + T cells. STxB therefore appears to be a powerful carrier directly targeting DC in vivo, resulting in a strong and durable CTL response associated with tumor protection.

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“…We have previously shown that STxB efficiently targets exogenous peptides into the MHC class I and II pathways and delivers Ag in vivo directly to DCs, which preferentially expressed the Gb 3 receptor (25)(26)(27). STxBbased vaccine induced humoral response (27,28) and a robust and long-lasting CD8 ϩ T cell response (27,29). All these results were obtained without the use of adjuvants and may be explained by the ability of STxB to increase costimulatory and MHC class II molecules on DCs (30) and to induce TNF-␣ on some cells (31), which could indirectly promote maturation of DCs.…”

mentioning

confidence: 99%

B Subunit of Shiga Toxin-Based Vaccines Synergize with α-Galactosylceramide to Break Tolerance against Self Antigen and Elicit Antiviral Immunity

Adotévi

Vingert

Freyburger

et al. 2007

The Journal of Immunology

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The nontoxic B subunit of Shiga toxin (STxB) targets in vivo Ag to dendritic cells that preferentially express the glycolipid Gb3 receptor. After administration of STxB chemically coupled to OVA (STxB-OVA) or E7, a polypeptide derived from HPV, in mice, we showed that the addition of α-galactosylceramide (α-GalCer) resulted in a dramatic improvement of the STxB Ag delivery system, as reflected by the more powerful and longer lasting CD8+ T cell response observed even at very low dose of immunogen (50 ng). This synergy was not found with other adjuvants (CpG, poly(I:C), IFN-α) also known to promote dendritic cell maturation. With respect to the possible mechanism explaining this synergy, mice immunized with α-GalCer presented in vivo the OVA257–264/Kb complex more significantly and for longer period than mice vaccinated with STxB alone or mixed with other adjuvants. To test whether this vaccine could break tolerance against self Ag, OVA transgenic mice were immunized with STxB-OVA alone or mixed with α-GalCer. Although no CTL induction was observed after immunization of OVA transgenic mice with STxB-OVA, tetramer assay clearly detected specific anti-OVA CD8+ T cells in 8 of 11 mice immunized with STxB-OVA combined with α-GalCer. In addition, vaccination with STxB-OVA and α-GalCer conferred strong protection against a challenge with vaccinia virus encoding OVA with virus titers in the ovaries reduced by 5 log compared with nonimmunized mice. STxB combined with α-GalCer therefore appears as a promising vaccine strategy to more successfully establish protective CD8+ T cell memory against intracellular pathogens and tumors.

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Oral immunization with a shiga toxin B subunit::rotavirus NSP490 fusion protein protects mice against gastroenteritis

Cited by 23 publications

References 27 publications

Rotavirus vaccines and pathogenesis: 2008

Rotavirus vaccines and pathogenesis: 2008

The Shiga toxin B‐subunit targets antigen in vivo to dendritic cells and elicits anti‐tumor immunity

B Subunit of Shiga Toxin-Based Vaccines Synergize with α-Galactosylceramide to Break Tolerance against Self Antigen and Elicit Antiviral Immunity

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