Identification of mechanisms conferring an enhanced immune response in mice induced by CVC1302-adjuvanted killed serotype O foot-and-mouth virus vaccine

Du, Lanying; Yu, Xiaoming; Hou, Liting; Zhang, Dong; Zhang, Yuanpeng; Qiao, Xuwen; Hou, Jingbo; Chen, Jin; Zheng, Qi

doi:10.1016/j.vaccine.2019.09.014

Cited by 6 publications

(9 citation statements)

References 46 publications

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“…In our previous study, we found that KV-CVC1302 could induce long-term humoral immunity (up to 5 months) in mice and pigs ( 5 , 6 ). Because the mice and pigs in that study received only one dose of KV-CVC1302, LLPCs were considered to be the most likely mediators of the observed sustained antibody production ( 15 ).…”

Section: Resultsmentioning

confidence: 95%

“…As local events at injection sites represent critical steps towards mounting a robust immune response, we investigated the ability of CVC1302 to induce an immunocompetent microenvironment in our previous study ( 6 ). However, owing to the lack of an available FMDV-specific antibody, we had limited capacity to analyze the ability of NP+ APCs influx at the injection sites and translocation to the draining LNs in that work.…”

Section: Resultsmentioning

confidence: 99%

“…Each cell suspension was centrifuged at 400 × g for 5 min, resuspended in Dulbecco’s Modified Eagle’s Medium (DMEM; Gibco), filtered through a 70-µm nylon mesh (BD Falcon, USA), and stained with fluorescently labeled antibodies for flow cytometric analysis. Single lymphocytes were harvested from draining LNs as previously reported ( 6 ). The lymphocytes were prepared using a Medimachine system with a Medicon (50 µm) disaggregator (BD Biosciences, San Diego, CA, USA) and stained with fluorescently labeled antibodies for flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous study found that immunization with killed FMDV vaccine adjuvanted with CVC1302 induces the establishment of an immunocompetent microenvironment at the injection site, which promotes the recruitment of APCs, especially dendritic cells (DCs) ( 6 ). However, owing to the lack of available fluorescently labeled FMDV- specific antibodies, we were unable to assess the ability of CVC1302 to promote the levels of antigen-positive APCs infiltrated in the injection sites and draining LNs in that previous study.…”

Section: Introductionmentioning

confidence: 99%

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Pattern-Recognition Receptor Agonist-Containing Immunopotentiator CVC1302 Boosts High-Affinity Long-Lasting Humoral Immunity

Hou

et al. 2021

Front. Immunol.

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Ideally, a vaccine should provide life-long protection following a single administered dose. In our previous study, the immunopotentiator CVC1302, which contains pattern- recognition receptor (PRR) agonists, was demonstrated to prolong the lifetime of the humoral immune response induced by killed foot-and-mouth disease virus (FMDV) vaccine. To elucidate the mechanism by which CVC1302 induces long-term humoral immunity, we used 4-hydroxy-3-nitrophenylacetyl (NP)-OVA as a pattern antigen and administered it to mice along with CVC1302, emulsified together with Marcol 52 mineral oil (NP-CVC1302). From the results of NP-specific antibody levels, we found that CVC1302 could induce not only higher levels of NP-specific antibodies but also high-affinity NP-specific antibody levels. To detect the resulting NP-specific immune cells, samples were taken from the injection sites, draining lymph nodes (LNs), and bone marrow of mice injected with NP-CVC1302. The results of these experiments show that, compared with mice injected with NP alone, those injected with NP-CVC1302 had higher percentages of NP+ antigen-presenting cells (APCs) at the injection sites and draining LNs, higher percentages of follicular helper T cells (TFH), germinal center (GC) B cells, and NP+ plasma-blasts in the draining LNs, as well as higher percentages of NP+ long-lived plasma cells (LLPCs) in the bone marrow. Additionally, we observed that the inclusion of CVC1302 in the immunization prolonged the lifetime of LLPCs in the bone marrow by improving the transcription expression of anti-apoptotic transcription factors such as Mcl-1, Bcl-2, BAFF, BCMA, Bax, and IRF-4. This research provides a blueprint for designing new generations of immunopotentiators.

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pattern-Recognition Receptor Agonist-Containing Immunopotentiator CVC1302 Boosts High-Affinity Long-Lasting Humoral Immunity

Hou

et al. 2021

Front. Immunol.

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“…Higher relative quantities of IFN-γ, IFN-α and IFN-β mRNA were detected in mice immunized with OVA-CVC1302-M52 than in those immunized with OVA-CVC1302. Furthermore, in our previous study, it was demonstrated that CVC1302 downregulated the expression of Nmi, which was responsible for negative regulation of type I IFN(21). Using flow cytometry, we confirmed that CXCL10 predominatly originated from Mo.…”

Section: Discussionmentioning

confidence: 99%

Conventional dendritic cells 2, the targeted antigen-presenting-cell, induces enhanced type 1 immune responses in mice immunized with CVC1302 in oil formulation

Qiao

Zhang

et al. 2022

Preprint

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Multifunctional CD4+T helper 1 (Th1) cells, producing IFN-γ, TNF-α and IL-2, define a correlate of vaccine-mediated protection against intracellular infection. In our previous study, we found that CVC1302 in oil formulation promoted the differentiation of IFN-γ+/TNF-α+/IL-2+Th1 cells. In order to extend the application of CVC1302 in oil formulation, this study aimed to elucidate the mechanism of action in improving the Th1 immune response. Considering the signals required for the differentiation of CD4+T cells to Th1 cells, we detected the distribution of innate immune cells and the model antigen OVA-FITC in lymph node (LN), as well as the quantity of cytokines produced by the innate immune cells. The results of these experiments show that, cDC2 and OVA-FITC localized to inter-follicular region (IFR) of the draining lymph nodes, inflammatory monocytes localized to both IFR and T cell zone, which mainly infiltrate from the blood. In this inflammatory niche within LN, CD4+T cells were attracted into IFR by CXCL10, secreting by inflammatory monocytes, then activated by IL-12-secreting cDC2. Above all, CVC1302 in oil formulation, on the one hand, targeted antigen and inflammatory monocyte into the LN IFN in order to attract CD4+T cells, on the other hand, targeted cDC2 to produce IL-12 in order to promote optimal Th1 differentiation. The new finding will provide a blueprint for application of immunopotentiators in optimal formulations.

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Conventional dendritic cells 2, the targeted antigen-presenting-cell, induces enhanced type 1 immune responses in mice immunized with CVC1302 in oil formulation

Du,

Lu,

Qiao

et al. 2024

Immunology Letters

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Identification of mechanisms conferring an enhanced immune response in mice induced by CVC1302-adjuvanted killed serotype O foot-and-mouth virus vaccine

Cited by 6 publications

References 46 publications

Pattern-Recognition Receptor Agonist-Containing Immunopotentiator CVC1302 Boosts High-Affinity Long-Lasting Humoral Immunity

Pattern-Recognition Receptor Agonist-Containing Immunopotentiator CVC1302 Boosts High-Affinity Long-Lasting Humoral Immunity

Conventional dendritic cells 2, the targeted antigen-presenting-cell, induces enhanced type 1 immune responses in mice immunized with CVC1302 in oil formulation

Conventional dendritic cells 2, the targeted antigen-presenting-cell, induces enhanced type 1 immune responses in mice immunized with CVC1302 in oil formulation

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