Topical CpG Adjuvantation of a Protein-Based Vaccine Induces Protective Immunity to Listeria monocytogenes

Cheng, Wing Ki; Wee, Kathleen; Kollmann, Tobias R.; Dutz, Jan P.

doi:10.1128/cvi.00734-13

Cited by 12 publications

(14 citation statements)

References 60 publications

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“…), 7 intravenous (i.v. ), 8 and subcutaneous (s.c.) 9 routes. Although many reports have demonstrated that CpG-ODNs can be used at doses greater than 100 μg in mice, there are few reports of oral (i.e., intragastric (i.g.))…”

Section: Introductionmentioning

confidence: 99%

Inhibitory/Suppressive Oligodeoxynucleotide Nanocapsules as Simple Oral Delivery Devices for Preventing Atopic Dermatitis in Mice

et al. 2015

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Here, we report a simple and low-cost oral oligodeoxynucleotide (ODN) delivery system targeted to the gut Peyer's patches (PPs). This system requires only Dulbecco's modified eagle's medium, calcium chloride, ODNs, and basic laboratory equipment. ODN nanocapsules (ODNcaps) were directly delivered to the PPs through oral administration and were taken up by macrophages in the PPs, where they induced an immune response. Long-term continuous oral dosing with inhibitory/suppressive ODNcaps (iODNcaps, "iSG3caps" in this study) was evaluated using an atopic dermatitis mouse model to visually monitor disease course. Administration of iSG3caps improved skin lesions and decreased epidermal thickness. Underlying this effect is the ability of iSG3 to bind to and prevent phosphorylation of signal transducer and activator of transcription 6, thereby blocking the interleukin-4 signaling cascade mediated by binding of allergens to type 2 helper T cells. The results of our iSG3cap oral delivery experiments suggest that iSG3 may be useful for treating allergic diseases.

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Section: Introductionmentioning

confidence: 99%

Inhibitory/Suppressive Oligodeoxynucleotide Nanocapsules as Simple Oral Delivery Devices for Preventing Atopic Dermatitis in Mice

et al. 2015

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“…Since ecCpG adjuvant was superior to subcutaneous CpG ODN (scCpG) adjuvant in providing protective immunity to L. monocytogenes ( 38 ), we further assessed whether ecCpG adjuvant is superior to scCpG adjuvant in providing protection from IAV. Mice were immunized with either scOVA and scCpG, or scOVA and ecCpG.…”

Section: Resultsmentioning

confidence: 99%

“…Topical adjuvant CpG ODN generated a robust antigen-specific CTL response when administered with the OVA protein model antigen ( 37 ). Enhanced specific immune responses can protect against subsequent Listeria monocytogenes infection ( 38 ). Importantly, the route of application was critical for CpG ODN to optimally boost T cell responses.…”

Section: Introductionmentioning

confidence: 99%

Topical CpG Oligodeoxynucleotide Adjuvant Enhances the Adaptive Immune Response against Influenza A Infections

et al. 2016

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Current influenza vaccines generate humoral immunity, targeting highly variable epitopes and thus fail to achieve long-term protection. T cells recognize and respond to several highly conserved epitopes across influenza serotypes. A strategy of raising strong cytotoxic T cell memory responses to epitopes conserved across serotypes would provide cross serotype protection, eliminating the need for annual vaccination. We explored the adjuvant potential of epicutaneous (ec) and subcutaneous (sc) delivery of CpG oligodeoxynucleotide in conjunction with sc protein immunization to improve protection against influenza A virus (IAV) infections using a mouse model. We found enhanced long-term protection with epicutaneous CpG ODN (ecCpG) compared to subcutaneous CpG ODN (scCpG) as demonstrated by reduced viral titers in the lungs. This correlated with increased antigen-specific CD8 T cells in the airways and the lungs. The memory T cell response after immunization with ecCpG adjuvant was comparable to memory response by priming with IAV infection in the lungs. In addition, ecCpG was more efficient than scCpG in inducing the generation of IFN-γ producing CD4 T cells. The adjuvant effect of ecCpG was accompanied with its ability to modulate tissue-homing molecules on T cells that may direct them to the site of infection. Together, this work provides evidence for using ecCpG to induce strong antibody and memory T cell responses to confer protection against IAV infection.

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“…Further investigation is required to develop a viable tumor vaccine from a vaccine candidate or candidate epitope. In future studies, the immunogenicity may be enhanced by exchanging certain amino acids, synthesizing a four-branch multiple antigenic peptide that may not require a carrier protein (23,24) and selecting a suitable adjuvant (25).…”

Section: Discussionmentioning

confidence: 99%

Peptide mimics of a carbohydrate-associated epitope expressed by cancer cells: Identification of vaccine candidates

Wen

Yang

Zhu

et al. 2016

Molecular Medicine Reports

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Cancer-associated antigen 215 (CA215) is an immunoglobulin molecule expressed by numerous tumor types. Membrane‑bound and soluble CA215 have been detected in the majority of cancer cells and rarely identified in normal tissues. In addition, CA215C is a carbohydrate‑associated epitope in the variable region of CA215, which is specifically recognized by the monoclonal antibody, RP215. However, CA215C is not a suitable vaccine candidate as it is a thymus‑independent antigen. In the present study, RP215 was used as a target to screen short peptide mimics of CA215C from a phage display peptide library. Following three rounds of screening, 30 positive phage clones that specifically bound to RP215 were identified and sequenced. The result of amino‑acid sequence analysis revealed five conserved sequence groups for seventeen of the positive phage clones. The sequences of phage clones 2, 13 and 42 were selected for peptide synthesis and binding analysis. The synthetic peptides R2 and R42 specifically bound RP215. Antisera from mice immunized with R2‑BSA or R42‑BSA bound purified CA215C and innate CA215C expressed on human hepatic and rectal carcinoma tissues, as demonstrated by immunohistochemistry. Furthermore, R2‑BSA and R42‑BSA antisera inhibited RP215 binding to cancer tissues. These results revealed that R2‑BSA and R42‑BSA antisera had similar characteristics to RP215 and that the synthetic peptides R2 and R42 may mimic the CA215C epitope. R2 and R42 peptides may therefore have potential for development into a tumor vaccine.

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Topical CpG Adjuvantation of a Protein-Based Vaccine Induces Protective Immunity to Listeria monocytogenes

Cited by 12 publications

References 60 publications

Inhibitory/Suppressive Oligodeoxynucleotide Nanocapsules as Simple Oral Delivery Devices for Preventing Atopic Dermatitis in Mice

Inhibitory/Suppressive Oligodeoxynucleotide Nanocapsules as Simple Oral Delivery Devices for Preventing Atopic Dermatitis in Mice

Topical CpG Oligodeoxynucleotide Adjuvant Enhances the Adaptive Immune Response against Influenza A Infections

Peptide mimics of a carbohydrate-associated epitope expressed by cancer cells: Identification of vaccine candidates

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