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poly(I:C)
Fish and Shellfish Immunology Reports · 2021 · IF 0

Feeding with poly(I:C) induced long-term immune responses against bacterial infection in turbot (Scophthalmus maximus)

Jing He,Zhuang Wang,Yanbo Zhao,Jin Yang,Yuanxing Zhang,Qin Liu,Dahai Yang

Poly(I:C) is a kind of chemosynthetic double-stranded RNA (dsRNA) analogue which could act as TLR3 agonist and induce IFN production. It is widely applied in anti-virus treatment and immunoregulation, as well as vaccine adjuvant in farmed animals. However, whether poly(I:C) could activate innate immune response to defense against bacterial infection remains unclear. In this study, we established a feeding trial model with different dose of poly(I:C) in turbot larvae, then challenged with Edwardsiella piscicida after 3–7 weeks resting period. The results show that feeding turbot with poly(I:C) exhibited a stronger inflammatory response and antioxidant stress ability, and significantly elevated the survival rate within the decreased bacterial loads. Importantly, the bacterial infection-induced white feces in hindgut of turbot were significantly alleviated after poly(I:C) feeding, and this administration induced protection could last for about 7 weeks. Taken together, these findings indicate that feeding turbot with poly(I:C) could enhance a long-term intestinal mucosal immunity in response to bacterial infection, suggesting that poly(I:C) might be a promising immunostimulant in aquaculture.

研究领域: 水产养殖学 · 免疫学
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DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY · 2023 · IF 2.9

The expanded ISG12 family in zebrafish: ISG12.1 suppresses virus replication via targeting viral phosphoprotein

Jiahong Guo,Wenji Huang,Xin Zhao,Ning Ji,Kangyong Chen,Yanjie Shi,Jianhua Feng,Jun Zou,Junya Wang

In mammals, interferon (IFN)-stimulated genes (ISGs) play important roles in restricting the replication of viruses . However, the functions of many ISGs have not been investigated in fish. In this study, eight isg12 homologs (termed isg12.1-8 ) were identified in zebrafish and all contain a typical ISG12 family domain rich of hydrophobic amino acid residues. Isg12.1-7 were significantly induced in the ZF4 cells by poly(I:C) and IFNφ1, and in the kidney and spleen after infection with spring viremia of carp virus (SVCV). In the EPC cells, overexpression of isg12.1 inhibited SVCV replication. Further, it was found that zebrafish ISG12.1 interacted with SVCV phosphoprotein (SVCV–P) and promoted SVCV-P degradation which could be attenuated by 3-MA and CQ (autophagy inhibitors). Our results indicate that zebrafish ISG12.1 restricts viral replication by targeting viral phosphoprotein for degradation.

CAS / MDL: 133407-82-6 5142-23-4
研究领域: 分子生物学 · 病毒学 · 免疫学
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International Journal of Nanomedicine · 2022 · IF 7.033

Exosomal Vaccine Loading T Cell Epitope Peptides of SARS-CoV-2 Induces Robust CD8+ T Cell Response in HLA-A Transgenic Mice

An-Ran Shen,Xiao-Xiao Jin,Tao-Tao Tang,Yan Ding,Xiao-Tao Liu,Xin Zhong,Yan-Dan Wu,Xue-Lian Han,Guang-Yu Zhao,Chuan-Lai Shen,Lin-Li Lv,Bi-Cheng Liu

Purpose Current vaccines for the SARS-CoV-2 virus mainly induce neutralizing antibodies but overlook the T cell responses. This study aims to generate an exosomal vaccine carrying T cell epitope peptides of SARS-CoV-2 for the induction of CD8 + T cell response. Methods Thirty-one peptides presented by HLA-A0201 molecule were conjugated to the DMPE-PEG-NHS molecules, and mixed with DSPE-PEG to form the peptide-PEG-lipid micelles, then fused with exosomes to generate the exosomal vaccine, followed by purification using size-exclusion chromatography and validation by Western blotting, liquid nuclear magnetic resonance (NMR) test and transmission electron microscopy. Furthermore, the exosomal vaccine was mixed with Poly (I:C) adjuvant and subcutaneously administered for three times into the hybrid mice of HLA-A0201/DR1 transgenic mice with wild-type mice. Then, the epitope-specific T cell responses were detected by ex vivo ELISPOT assay and intracellular cytokine staining. Results The exosomal vaccine was purified from the Peak 2 fraction of FPLC and injected into the hybrid mice for three times. The IFN-γ spot forming units and the frequencies of IFN-γ + /CD8 + T cells were 10–82-fold and 13–65-fold, respectively, higher in the exosomal vaccine group compared to the Poly (I:C) control group, without visible organ toxicity. In comparison with the peptides cocktail vaccine generated in our recent work, the exosomal vaccine induced significantly stronger T cell response. Conclusion Exosomal vaccine loading T cell epitope peptides of SARS-CoV-2 virus was initially generated without pre-modification for both peptides and exosomes, and elicited robust CD8 + T cell response in HLA-A transgenic mice.

CAS / MDL: 121-44-8
研究领域: 免疫学 · 病毒学 · 分子生物学 · 疫苗研究
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MICROBIAL PATHOGENESIS · 2021 · IF 3.738

A new poly(I:C)-decorated PLGA-PEG nanoparticle promotes Mycobacterium tuberculosis fusion protein to induce comprehensive immune responses in mice intranasally

Xiufen Du,Daquan Tan,Yang Gong,Yifan Zhang,Jiangyuan Han,Wei Lv,Tao Xie,Pu He,Zongjie Hou,Kun Xu,Jiying Tan,Bingdong Zhu

Protein-based subunit vaccine against tuberculosis (TB) is regarded as safer but with lower immunogenicity . To investigate effective adjuvant to improve the immunogenicity of TB subunit vaccine, we modified ploy(I:C) onto PLGA-PEG copolymer nanoparticle with polydopamine to produce a new nanoparticle adjuvant named “PLGA-PEG-poly(I:C)” (NP). M. tuberculosis fusion proteins Mtb10.4-HspX and ESAT-6-Rv2626c (M4) were encapsulated in the nanoparticles to produce the NP/M4 subunit vaccine. The PLGA-PEG/M4 nanoparticle was 200.21 ± 1.07 nm in diameter, and the polydispersity index (PDI) was 0.127 ± 0.02. Following modification with poly(I:C) by polydopamine, the NP/M4 was administered to C57BL/6 female mice intranasally and the immune responses were evaluated. The NP/M4 significantly induced antigen-specific CD4 + T cells proliferation, IL-2 and IFN-γ production. In addition, the NP/M4 could promote the production of antigen-specific IgG, IgG1 , IgG2c in serum, and sIgA in lung washings . Overall, our results indicated that the NP would be a potential TB subunit vaccine adjuvant with the ability to induce strong Th1-type cell-mediated immunity and humoral immune responses .

研究领域: 免疫学 · 疫苗学 · 纳米技术 · 结核病
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PHYTOMEDICINE · 2026 · IF 8.3

Complementary Roles and Synergy of the Ephedra-Glycyrrhiza Herb Pair Across Murine Models of Respiratory Symptoms and Poly(I:C)-Induced Pneumonia

Fan Zhang,Yajie Ma,Jie Mei,Xinrong Xie,Xiaoyan Wang,Yuanyuan Zhang,Boyang Yu

Background The Ephedrae herba (Eh)-Glycyrrhizae Radix et Rhizoma(Grr) herb pair (EGP) is used for viral respiratory illness, but its advantage over single herbs and mechanistic basis remain unclear. Purpose To define the complementary roles and synergistic mechanisms of Eh and Grr within EGP and to assess short-term oral tolerability. Methods Anti-inflammatory, antipyretic, antitussive, and expectorant effects of Eh, Grr, and EGP were evaluated in four corresponding murine models, and synergy was quantified with the Bliss independence model. Single-cell RNA sequencing and bioinformatics were used to implicate relevant cell types and pathways. Key findings were confirmed in Poly(I:C)-stimulated RAW 264.7 cells and lung tissue by ELISA, qPCR, Western blotting, and immunofluorescence. A 7-day oral study evaluated general condition, body weight, serum chemistry, organ indices, and histology. Results EGP improved fever, cough, sputum clearance, and pulmonary inflammation. Antitussive/expectorant effects were predominantly associated with Grr, antipyretic effects mainly with Eh, and both herbs contributed to anti-inflammatory activity. The combination showed synergistic anti-inflammatory effects, with greater interleukin-1β (IL-1β) suppression than either herb alone. p38 MAPK and NF-κB p65 phosphorylation was reduced, and co-inhibition of p38 MAPK and NF-κB ameliorated lung-injury indices and systemic cytokines beyond single inhibitors. No overt toxicity was observed under the 7-day oral dosing conditions at the tested doses. Conclusions EGP shows complementary roles in symptom control—Grr providing antitussive and expectorant effects and Eh antipyretic activity—and synergistic anti-inflammatory action centred on IL-1β, with good short-term oral tolerability in mice.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMATERIALS · 2022 · IF 15.304

A peptide-AIEgen nanocomposite mediated whole cancer immunity cycle-cascade amplification for improved immunotherapy of tumor

Jun Dai,Xiaoqi Dong,Rui Liu,Biao Chen,Xiyuan Dong,Quan Wang,Jing-Jing Hu,Fan Xia,Xiaoding Lou

Immunotherapy maintains the cancer-immunity cycle via re-activating the immune system, so as to achieve the purpose of anti-tumor. However, the response rate of current tumor immunotherapy strategies is still low. Even the most reported immune checkpoint block (ICB), the objective response rate (ORR) is only about 10–30%. Here, aiming at obtaining a higher response rate, we designed a cascade amplification nanocomposite consisting of the immune adjuvant polyinosinic:polycytidylic acid [Poly (I:C)] and aggregation-induced emission luminogen (AIEgen)-modified modular peptide (named PMRA). The PMRA includes: D PPA-1 peptide (P), an immune checkpoint inhibitor; PLGLAG peptide (M), a matrix metalloproteinase 2 (MMP-2) responsive sequence to promote the release of D PPA-1; RRRRRRRR peptide (R), for loading the Poly (I:C); PyTPA (A), a photosensitizer with AIE property. In cancer-immunity cycle, photodynamic therapy (PDT) mediated by PyTPA promotes the release of tumor-associated antigens (TAAs), and primes T lymphocytes . The cytokines coming from the stimulation of PDT and Poly (I:C) promote the activation of T lymphocytes. The high level of chemokines in tumor microenvironment promotes immune cells migration and infiltration in tumor with the assistance of PDT. Finally, through ICB with D PPA-1 peptide, T lymphocytes enhance the recognition of tumor cells and killing tumor cells. Immunogenic cell death induces the release of more TAAs, which will enter the next cycle and complete the full-loop again. Taking advantages of whole cancer-immunity cycle, the cascade amplification nanocomposite achieved almost 100% ORR in vivo . This concept of whole cancer-immunity cycle enhanced immunotherapy provides a novel perspective for tumor treatment.

CAS / MDL: 2044-85-1
研究领域: 癌症生物学 · 免疫学 · 纳米技术 · 治疗学
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