EBioMedicine
·
2022
·
IF 11.205
Mengyi Zhang,Yimeng An,Xi Wu,Meina Cai,Xinyu Zhang,Chaoying Yang,Jincheng Tong,Zhimin Cui,Xueli Li,Weijin Huang,Chenyan Zhao,Youchun Wang
Summary Background Influenza A (H3N2) virus (A/H3N2) has complex antigenic evolution, resulting in frequent vaccine strain updates. We aimed to evaluate the protective effect of the vaccine strains on the circulating strains from past ten years and provide a basis for finding a broader and more efficient A/H3N2 vaccine strain. Methods Eighty-four representative circulating A/H3N2 strains were selected from 65,791 deposited sequences in 2011–2020 and pseudotyped viruses were constructed with the VSV vector. We immunized guinea pigs with DNA vaccine containing the A/H3N2 components of the vaccine strains from 2011 to 2021 and tested neutralizing antibody against the pseudotyped viruses. We used a hierarchical clustering method to classify the eighty-four representative strains into different antigenic clusters. We also immunized animals with monovalent vaccine stock of the vaccine strains for the 2020–2021 and 2021–2022 seasons and tested neutralizing antibody against the pseudotyped viruses. Findings The vaccine strains PE/09, VI/11 and TE/12 induced higher levels of neutralizing antibody against representative strains circulating in recommended year and the year immediately prior whereas vaccine strains HK/14, HK/19 and CA/20 induced poor neutralization against all representative strains. The representative strains were divided into five antigenic clusters (AgV), which were not identical to gene clades. The AgV5 strains were most difficult to be protected among the five clusters. Compared with single-dose immunization, three doses of monovalent vaccine stock (HK/19 or CA/20) could induce stronger and broader neutralizing antibodies against strains in each of the antigenic clusters. Interpretation The protective effect of vaccine strains indicated that the accurate selection of A/H3N2 vaccine strains must remain a top priority. By increasing the frequency of immunization, stronger and broader neutralizing antibodies against strains in all antigenic clusters were induced, which provides direction for a new immunization strategy. Funding This work was supported by a grant from National Key R&D Program of China (No. 2021YFC2301700 ).
研究领域:
病毒学
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免疫学
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流行病学
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DOI
PubMed
高影响因子
VETERINARY MICROBIOLOGY
·
2021
·
IF 3.293
Jingjing Qi,Yu Wang,Haoran Li,Yuanbing Shang,Song Gao,Chan Ding,Xiaohan Liu,Shaohui Wang,Tao Li,Mingxing Tian,Shengqing Yu
Mycoplasma synoviae ( M. synoviae ) is an important avian pathogen that causes arthritis and airsacculitis in young chickens and turkeys. Infection by M. synoviae results in considerable economic losses to the poultry industry worldwide. Cytoadherence is a crucial stage during mycoplasma infection. Dihydrolipoamide dehydrogenase (PdhD) is a flavin-dependent enzyme that is critical for energy metabolism and redox balance. To date, its role in cytoadherence is poorly understood. In this study, recombinant PdhD from M. synoviae (rMSPdhD) was expressed in the supernatant component of E. coli BL21 and rabbit anti-rMSPdhD serum was prepared. rMSPdhD was shown to be an immunogenic protein by immunoblot assays, while the mycoplasmacidal assay revealed that the rabbit anti-rMSPdhD serum had a high complement-dependent mycoplasmacidal rate (88.5 %). Using a suspension immunofluorescence assay and subcellular localization analysis, MSPdhD was shown to be a surface-localized protein distributed in both the cytoplasm and cell membrane of M. synoviae . The enzymatic activity of rMSPdhD was determined by measuring its ability to reduce lipoamide to dihydrolipoamide and convert NADH to NAD + . Using an indirect immunofluorescence assay, rMSPdhD was shown to adhere to DF-1 chicken embryo fibroblast cells. Furthermore, the attachment of M. synoviae to DF-1 cells was significantly inhibited by rabbit anti-rMSPdhD serum. Western blot and ELISA binding assays confirmed that rMSPdhD also bound to fibronectin (Fn) and plasminogen (Plg) in a dose-dependent manner. In conclusion, our data show that MSPdhD is not only a biological enzyme, but also an immunogenic surface-exposed protein that can bind to Fn and Plg as well as adhere to host cells. In addition, we show that rabbit anti-rMSPdhD serum can inhibit the adhesion of M. synoviae to DF-1 cells and has a significant complement-dependent bactericidal activity. Our findings suggest that MSPdhD may be involved in the pathogenesis of M. synoviae .
研究领域:
微生物学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
Mengzi Hu,Yaqiong Wang,Xue-Bo Yin
In addition to the robust adhesive properties, there is a pressing demand for ideal adhesives in tumor surgery that possess anti-tumor therapeutic effects. In this study, we introduce BSA-MnO 2 -GP@Ca-Y (BMGY) bio-glue by integrating bovine serum albumin (BSA)-MnO 2 , genipin (GP), and Ca-Y zeolite. Ca-Y zeolite exhibits the thrombin activity for hemostasis, while the cross-linking of BSA, GP, and skin tissue induces wound adherence upon laser irradiation for normalized skin structure within nine days. The heat generated during the “photothermal suture” process ablates residual tumor cells and produces antigen fragments, which are internalized by antigen presenting cells. The released Mn ions subsequently activate the cGAS-STING pathway, enhancing immunogenicity. Consequently, tumor-infiltrating p-TBK1 and interferon-β levels are significantly increased, ensuring robust anti-tumor immunity following BMGY treatment. Thus, BMGY bio-glue achieves hemostasis, wound bonding, ablation of residual tumor cells, and tumor recurrence inhibition, simultaneously. Beyond Ca-Y zeolite, BSA-MnO 2 -GP serves as a versatile platform for loading other drugs or active species to boost therapeutic efficacy. Therefore, we present a successful bio-glue paradigm with significant translational potential for various postsurgical management applications.
研究领域:
生物医学工程
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肿瘤免疫学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Qing Guan,Junjie Chen,Zhaonan Liu,Jianfeng Xin,Yu Chen,Peng Wang,Jun Liu
Bacteria possess distinctive characteristics, such as tropism, motility, and genetic editability, which make them highly attractive for biomedical applications, such as tumor imaging and therapy. However, the immunogenicity triggered by endotoxins may lead to severe adverse effects and prompt quick elimination in the body, thus restricting their clinical applications. In this study, we described a double-layer coating technique employing tannic acid (TA) and albumin (BSA) for bacteria encapsulation. This compact coating effectively shields endotoxin exposure and inhibits endotoxin leakage from bacteria, exhibiting a favorable safety profile. Moreover, bacteria coated with BSA have superior biocompatibility with their surroundings, which prevents phagocytes from eliminating the bacteria, hence prolonging the reservation in vivo. As bacteria grow, the BSA-TA layer progressively detaches after reaching targeted sites, allowing free bacteria to exploit their own advantages. Importantly, the BSA-TA coating strategy protects bacteria against various environmental assaults without compromising their growth, proliferation, or motility, maintaining their inherent characteristics. In murine tumor models, the BSA-TA-coated bacteria demonstrated enhanced long-term tumor imaging and therapeutic efficacy against tumors. Together, the BSA-TA coating strategy improves the biocompatibility of bacteria and has the capacity to expand the range of bacteria for biomedical applications. A double-layer coating technique using tannic acid and albumin is developed for bacterial encapsulation, which camouflages bacteria to extend the reservation time in vivo and prevents endotoxin exposure and release, showing potent biocompatibility. Meanwhile, the inherent properties of bacteria are retained. This technology shows excellent tumor targeting, long-term tumor imaging, and potent anti-tumor therapeutic efficacy.
研究领域:
医学
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生物技术
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
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IF 9.4
Ming-Chao Jiang,Zhou-Long Fang,Jin-Yan Zhang,Wei Ma,Luan-Feng Liao,Cui-Yun Yu,Hua Wei
Facile construction of a fully biodegradable spherical nucleic acid (SNA) nanoplatform is highly desirable for clinical translations but remains rarely explored. We developed herein the first polycarbonate-based biodegradable SNA nanoplatform for self-codelivery of a chemotherapeutic drug, doxorubicin (DOX), and a human liver-specific miR122 for synergistic chemo-gene therapy of hepatocellular carcinoma (HCC). Ring-opening polymerization (ROP) of a carbonate monomer leads to a well-defined polycarbonate backbone for subsequent DOX conjugation to the pendant side chains via acidic pH-cleavage Schiff base links and miR122 incorporation to the chain termini via click coupling, affording an amphiphilic polycarbonate-DOX-miR122 conjugate, PBis-Mpa 30 -DOX-miR122 that can self-assemble into stabilized SNA. Besides the desired biodegradability, another notable merit of this nanoplatform is the use of miR122 not only for gene therapy but also for enhanced innate immune response. Together with the ICD-triggering effect of DOX, PBis-Mpa 30 -DOX-miR122 SNA-mediated DOX and miR122 codelivery leads to synergistic immunogenicity enhancement, resulting in tumor growth inhibition value (TGI) of 98.1 % significantly higher than those of the groups treated with only drug or gene in a Hepa1-6-tumor-bearing mice model. Overall, this study develops a useful strategy toward biodegradable SNA construction, and presents a drug and gene-based self-codelivery SNA with synergistic immunogenicity enhancement for efficient HCC therapy. Statement of significance Facile construction of a fully biodegradable SNA nanoplatform is useful for in vivo applications but remains relatively unexplored likely due to the synthetic challenge. We report herein construction of a polycarbonate-based SNA nanoplatform for co-delivering a chemotherapeutic drug, DOX, and a human liver-specific miR-122 for synergistic HCC treatment. In addition to the desired biodegradability properties, this SNA nanoplatform integrates DOX-triggered ICD and miR-122-enhanced innate immunity for simultaneously activating adaptive and innate immunities, which leads to potent antitumor efficiency with a TGI value of 98.1 % in a Hepa1-6-tumor-bearing mice model.
研究领域:
肿瘤学
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分子生物学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Pathogens
·
2022
·Vol. 11
·期 5
·550
·
IF 4.531
Jia-Li Yu,Qing-Yang Liu,Bo Yang,Yi-Fan Sun,Ya-Ju Wang,Jian Jiang,Bo Wang,Yang Cheng,Qiu-Bo Wang
Plasmodium falciparum, mainly distributed in tropical and subtropical regions of the world, has received widespread attention owing to its severity. As a novel protein,P. falciparumsurface-related antigen (PfSRA) has the structural and functional characteristics to be considered as a malaria vaccine candidate; however, limited information is available on its immunogenicity. Here, we expressed three fragments of recombinant PfSRA in anEscherichia colisystem and further analyzed its immunogenicity. The results showed that rPfSRA-immunized mice produced specific antibodies with high endpoint titers (1:10,000 to 1:5,120,000) and affinity antibodies (i.e., rPfSRA-F1a (97.70%), rPfSRA-F2a (69.62%), and rPfSRA-F3a (91.87%)). In addition, the sera of immunized mice recognized both the native PfSRA and recombinant PfSRA, the rPfSRA antibodies inhibited the invasion ofP. falciparuminto the erythrocytes, and they were dose-dependent in vitro. This study confirmed PfSRA could be immunogenic, especially the F1a at the conserved region N-terminal and provided further support for it as a vaccine candidate againstP.falciparum.Keywords:Plasmodium falciparum;surface-related antigen;immunogenicity;invasion inhibition
研究领域:
疟疾
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免疫学
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疫苗开发
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Xiaobo Yu,Jingli Ding,Yingjie He,Shunbo Wei,Xing Chen,Qiujie Luo,Yuqing Zhang,Chen Qian,Jiahui Wang,Mengjie Hu,Xiang Zhang,Cuifen Lu,Jinping Liu,Jianliang Zhou
Valvular heart disease (VHD) poses a thorny problem in cardiovascular diseases. The most effective treatment for VHD is heart valve replacement. Biological heart valve (BHV) is more favored than mechanical heart valve due to the maturity of transcatheter heart valve replacement (THVR) and the absence of the need for lifelong anticoagulant use. However, traditional commercial BHV suffers degeneration within 10 to 15 years because of calcification caused by the cross-linking reagent, glutaraldehyde. Considering the remarkable properties of POSS, PEG, and the star-like eight-arm structure, we fabricated POSS-PEG-PP, which is a decellularized porcine pericardium (DPP) crosslinked by a star-like eight-arm cross-linker octafunctionalized POSS of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO) based on the Schiff's base reaction. POSS-PEG-PP exhibits more intense fiber arrangement and better mechanical properties than GLUT-PP (glutaraldehyde crosslinked DPP). The results also show that the cytocompatibility, endothelialization, and hemocompatibility of POSS-PEG-PP are outstanding in vitro. Subsequently, in vivo assessments demonstrate that POSS-PEG-PP has anti-inflammatory and anti-calcification abilities. Furthermore, RNA sequencing analysis of subcutaneous implants suggests that the intervention of AMPK and IL-17 signaling pathways plays an important role in the inflammatory and immune responses regulation of POSS-PEG-PP. Therefore, POSS-PEG-PP is an excellent substitute material for BHVs and is expected to be clinically transformed.
研究领域:
心血管疾病
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生物材料科学
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组织工程
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产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2020
·Vol. 15
·期 6
·065012
·
IF 3.174
Yu Luo,Lie Ma
Despite the good hemodynamic characteristics of bioprosthetic heart valves, it is inevitable that they will suffer from calcification and tissue deterioration. Decellularization has been utilized to reduce the immunogenicity and calcification of bioprosthetic heart valves. However, it can take several days or even weeks to obtain the decellularized tissues or organs. Therefore, time-frame should be taken into consideration during the decellularization process. A detergent-enzymatic-method, combined with vacuum, has been proposed as a method of obtaining desirable decellularized heart valves. In this study, heart valves treated under vacuum and normal atmosphere are investigated via histological, biochemical and mechanical analysis. The results show that the decellularization efficiency of heart valves treated under vacuum is enhanced, based on histological staining, DNA contents and α-Gal quantification. The decellularization procedures decrease the contents of the extracellular matrix. However, the mechanical properties, including elastic modulus, fracture tensile strength and fracture strain, show no significant difference between the samples. In vitro cell cytotoxicity experiments indicate the feasibility of further in vivo experiments. Therefore, we conclude that vacuum-assisted decellularization procedures can significantly enhance decellularization efficiency by reducing the decellularization time, without compromising the properties of the heart valves, which is also beneficial in terms of reducing clinical costs. To the best of our knowledge, vacuum is a novel parameter which can be designed into decellularization procedures for heart valves.
研究领域:
生物医学工程
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心血管外科
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Dapeng Li,Yuanfan Li,Jie Cang,Xianwen Yan,Feipeng Wu,Xuan Sun,Wenchao Zhang
Introduction: Osteosarcoma (OS) is the most common primary malignant bone tumor in pediatric populations. Its treatment is complicated by chemotherapy-induced toxicity and limited induction of immunogenic cell death (ICD).Methods: To address these challenges, we developed a pH-responsive, multi-component nanoparticle system designed to co-deliver doxorubicin (DOX), monophosphoryl lipid A (MPLA), and a PD-1/PD-L1-targeting peptide, integrated with the immune-modulating polymer PEG-PC7A. The system was optimized using both one-factor-at-a-time (OFAT) and Box-Behnken design (BBD).Results: The optimized nanoparticles had a hydrodynamic size of 110 nm, high encapsulation efficiency (97.15%), and pH-sensitive drug release (91% at pH 6.5). In vitro studies showed enhanced ICD markers, including calreticulin exposure and ATP/HMGB1 release, aswell as synergistic dendritic cell maturation via dual STING/TLR4 pathway activation. In an orthotopic LM8 osteosarcoma model, the nanoparticles significantly suppressed tumor growth, promoted cytotoxic T lymphocyte infiltration, reduced regulatory T cells, and established long-term immune memory.Discussion: The combination of ICD induction, innate immune activation, and checkpoint blockade reprogrammed the tumor microenvironment, amplifying anti-tumor immune responses. These results demonstrate the potential of this multifunctional nanoparticle platform as an effective immunochemotherapeutic strategy for osteosarcoma, offering enhanced therapeutic efficacy and reduced systemic toxicity.
研究领域:
肿瘤学
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免疫学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Xikuang Yao,Changrui Sun,Fei Xiong,Weina Zhang,Wenjing Yao,Yinghui Xu,Wenpei Fan,Fengwei Huo
Nanomedicine-enhanced immunogenic cell death (ICD) has attracted considerable attention for its great potential in cancer treatment. Even though polyethylene glycol (PEG) is widely recognized as the gold standard for surface modification of nanomedicines, some shortcomings associated with this PEGylation, such as hindered cell endocytosis and accelerated blood clearance phenomenon, have been revealed in recent years. Notably, polysarcosine (PSar) as a highly biocompatible polymer can be finely synthesized by mild ring-opening polymerization (ROP) of sarcosine N-carboxyanhydrides (Sar-NCAs) and exhibit great potential as an alternative to PEG. In this article, PSar-b-polycamptothecin block copolymers are synthesized by sequential ROP of camptothecin-based NCAs (CPT-NCAs) and Sar-NCAs. Then, the detailed and systematic comparison between PEGylation and PSarylation against the 4T1 tumor model indicates that PSar decoration can facilitate the cell endocytosis, greatly enhancing the ICD effects and antitumor efficacy. Therefore, it is believed that this well-developed PSarylation technique will achieve effective and precise cancer treatment in the near future.
研究领域:
肿瘤学
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药剂学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xiangyan Chen,Guohua Ma,Junyao Li,Xintao Gao,Yantao Li
Combination therapy that promotes both apoptosis and immunogenic cell death (ICD) holds promise for enhanced tumor treatment, yet its effectiveness is often hindered by challenges including inadequate targeted delivery, intricate nanoformulations processes, and cost inefficiency. Here, we present novel tumor-targeted, stimuli-responsive nanomicelles (D@CGO-G) through a straightforward supramolecular self-assembly method, incorporating targeting peptide GE11, doxorubicin (DOX), and a labile carrageenan (CG) linkage. Mechanistic insights into nanomicelles assembly process are thoroughly investigated using molecular dynamics (MD) simulations. D@CGO-G exhibit superior targeting capability both in vitro and in vivo , while the released DOX induces tumors apoptosis and ICD, stimulating macrophage polarization and enhancing the infiltration of tumor cytotoxic T lymphocytes. Furthermore, D@CGO-G effectively suppress both primary and distant tumors in vivo through combined apoptosis and anti-tumor immune responses. Our results highlight a simple, cost-effective approach to develop responsive CG-based nanomicelles for precise tumor targeting and robust multimodal therapeutic effects, advancing their clinical potential in cancer therapy.
研究领域:
生物医学工程
·
药学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 2
·166
·
IF 5.5
Guangwei Jiang,Rong Huang,Min Qian,Wenjuan Hu,Rongqin Huang
Background: Photothermal therapy has the potential to enhance the precision and safety of oncological treatments. However, applicable photothermal agents associated with its photothermal activated immunogenic cell death remain exploiting.Methods: This study evaluates the effectiveness of IR813, a photothermal agent, combined with near-infrared (NIR) light for cancer treatment. In vitro, 4T1 cancer cells were treated with IR813 (5 μg/mL) and exposed to NIR irradiation (1 W/cm2) for 5 min. In vivo, after the tumor-bearing mice administered with IR813 (1 mg/kg) and exposed to NIR irradiation (1 W/cm2) for 10 min, the tumor volume, survival and immune activation were evaluated.Results: IR813 significantly increased the cytotoxicity of 4T1 cancer cells following near-infrared irradiation, resulting in the release of damage-associated molecular patterns and immunogenic cell death. Specifically, the cell viability was reduced to 5% compared to the control group. In vivo, irradiating the accumulation of IR813 at the tumor site had the potential to mediate substantial photothermal tumor suppression, improved mouse survival, and reduced metastasis, with minimal adverse reactions. Furthermore, the immune responses stimulated by IR813-induced photothermal therapy were evidenced by increased mature dendritic cell and cytotoxic T lymphocyte counts and a decrease in regulatory T cells in the spleen, tumor, and lymph nodes.Conclusions: These findings suggest that IR813-induced photothermal therapy is a promising approach for enhancing immunotherapy, directly inhibiting tumors while boosting systemic anti-cancer immunity.
研究领域:
肿瘤学
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免疫学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）