Vaccines
·
2021
·Vol. 9
·期 7
·786
·
IF 4.422
Linpei Guo,Hui Xie,Zheng Zhang,Zhun Wang,Shuanghe Peng,Yuanjie Niu,Zhiqun Shang
(1) Background: There are currently limited treatments for castration-resistant prostate cancer. Immunotherapy involving Sipuleucel-T has increasingly drawn attention for prostate cancer management. BCG plays a vital role in treating bladder cancer, mainly by inducing immune activation, but is rarely used for prostate cancer. (2) Methods: The TCGA database, PCR, and Western blotting were used to analyze the expression of STEAP1 in mouse and human tissues. Then, we constructed a fusion protein vaccine withMycobacterium tuberculosisAg85B and three repeated octapeptide epitopes of a six-transmembrane epithelial antigen of the prostate 1 (STEAP1186-193), Ag85B-3×STEAP1186-193. The uptake of the fusion protein vaccine by DCs was evaluated by confocal microscopy, and DC markers were detected using flow cytometry after incubation with the fusion protein. The immune response against prostate cancer was evaluated by the LDH assay and xenografts in vitro and in vivo. Then, the tumor microenvironment was determined using IHC and ELISA. In addition, the epitope was mutated using CRISPR-Cas9 to illustrate that the fusion protein elicited immunization against STEAP1. (3) Results: The TCGA database analysis, PCR, and Western blotting showed that STEAP1 was highly expressed in human and murine prostate cancer. After the uptake of the purified fusion protein vaccine by DCs, CD11c, CD80, CD86, and MHC II were upregulated and triggered a cytotoxic T lymphocyte (CTL) response against TRAMP-C1 and RM1 cells in vitro. Furthermore, the fusion protein vaccine inhibited tumor growth and improved the tumor microenvironment in vivo, with more CD3+cells and fewer FOXP3+cells in the tumor. Serum IFN-γ and IL-2 were significantly higher than in the control group, while IL-4 expression was lower, indicating that the fusion protein vaccine activated Th1 immunity. The immune response against prostate cancer was greatly suppressed when the antigen targets were knocked out using CRISPR-Cas9. (4) Conclusion: In summary, our results provide the first evidence that a vaccine based on a fusion protein consisting of Ag85B and a prostate cancer octapeptide epitope with complete Freund’s adjuvant (CFA), triggers a robust immune response and inhibits tumor growth in murine prostate cancer.Keywords:Ag85B;Mycobacteriumtuberculosis;STEAP1;six-transmembrane epithelial antigen of the prostate 1;immune response;prostate cancer;castration-resistant prostate cancer (CRPC)
研究领域:
肿瘤学
·
免疫学
·
分子生物学
·
癌症免疫疗法
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Zhen Wang,Zhangyi Miao,Zhiting Cao,Jianye Ren,Xiaohong Zhu,Yu Sheng,Hao Cheng,Huaqing Zhang,Jianping Zhou,Yang Ding
Epicutaneous immunotherapy (EPIT) is effective and safe to induce sustained protection against anaphylaxis with small doses of allergens. To penetrate the barrier of the stratum corneum, a coaxial nanofiber patch is designed that incorporates natural phase-change materials (PCM) for mild hyperthermia-assisted skin permeability, while minimizing the risk of systemic events during immunotherapy. For adaptive immune activation, Toll-like receptor 7/8 ligand of resiquimod (R848) is combined with ovalbumin (OVA) allergen, thereby stimulating the Th1 pathway and strengthening therapeutic efficacy. For sequential administration, coaxial electrospinning technology is utilized for multiple drug encapsulation and sequential release, where the shell layer consists of poly(vinyl alcohol) (PVA) with OVA dispersion, and the core region is a mixture of PCM and R848. Under mild hyperthermia irritation, the nanofiber patches perform an efficient immunomodulation by manipulating the skin immune system via allergen/adjuvant combinations, which inhibits the secretion of OVA-specific IgE, and improves lung functions sufficiently in a mouse model of allergic asthma. Mechanistically, the treatment favors IgG2a expression from a Th1-biased immune response and induces protective regulatory immunity against allergen exposure. Overall, the simplicity and potency of mild hyperthermia mediated EPIT qualifies as a translational strategy for IgE-mediated allergies with long-lasting curative effects.
研究领域:
生物医学工程
·
免疫治疗
·
纳米技术
·
药学
·
过敏与免疫学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Xiaoli Ling,Zhipeng Tian,Dong Chen,Yujia Zhang,Ziyan Dong,Dan He,Jiayu Li,Zhidi He,Jiaxin Li,Fang Chen,Qin He,Man Li
Self-adjuvanted vaccine delivery platforms possess potential for targeted delivery of antigens and initiation of potent immune responses. Although aluminum-containing adjuvants have been approved and widely used in human vaccines, their effectiveness in inducing Th1-type immune responses is far from satisfactory. To facilitate antigen delivery and activate potent antitumor immune responses, a self-adjuvanted nanovaccine (CPBG-Al@OVA) is constructed by functionalizing aluminum hydroxide with β-1,3-glucan, which recognizes pattern recognition receptors via Dectin-1. Carboxymethyl-phosphorylated β-1,3-glucan (CPBG) has been synthesized and optimized to achieve superior adjuvanticity while maintaining water solubility. CPBG then self-assembles with aluminum hydroxide and the targeted antigen, leading to the formation of a nanovaccine CPBG-Al@OVA. Owing to the favorable nanoscale size distribution, CPBG-Al@OVA effectively drains to the lymph nodes and is internalized by antigen-presenting cells (APCs) through Dectin-1-mediated endocytosis, activating the Syk and Raf1 signaling pathways and leading to upregulated TNFSF15 and OX40L expression to activate APCs. Following immunization, CPBG-Al@OVA activates potent CD8 + T cell and humoral responses to inhibit tumor growth. Notably, mice vaccinated with CPBG-Al@OVA showed extended survival, with more than 70 % of the mice surviving for over 50 days post-tumor challenge. Moreover, the CPBG-Al nanoparticle also possesses personalized immune-activating capacity by encapsulating tumor lysate as an antigen, specifically suppressing tumor growth. This strategy synergizes the adjuvant effects of aluminum and β-1,3-glucan, offering a platform for self-adjuvanted nanovaccine design with significant clinical translational potential.
研究领域:
免疫学
·
癌症研究
·
疫苗学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Anan Guo,Lvqing Tang,Bing Yang,Niling Xie,Yandong Cui,Wen Sun,Yuan Li,Xiangting Li,Yang Wu,Yingshuai Liu
Adjuvants including aluminum adjuvant (Alum) and oil-water emulsion have been widely used in inactivated pseudorabies virus (PRV) vaccines to improve their performance, however, they are not sufficient to protect from PRV infection because of the weak immune response and poor Th1-type immune response. Divalent manganese ion (Mn 2+ ) has been reported to increase the cellular immune response significantly. In this work, a xanthan gum and carbomer-dispersed Mn 2+ -loaded tannic acid-polyethylene glycol (TPMnXC) nanoparticle colloid is developed and used as an adjuvant to improve the performance of the inactivated PRV vaccine. The good in vitro and in vivo biocompatibility of the developed TPMnXC colloid has been confirmed by the cell viability assay, erythrocyte hemolysis, blood routine analysis, and histological analysis of mouse organs and injection site. The TPMnXC-adjuvanted inactivated PRV vaccine (TPMnXC@PRV) significantly promotes higher and more balanced immune responses indicating with an increased specific total IgG antibody and IgG2a/IgG1 ratio, efficient splenocytes proliferation, and elevated Th1- and Th2-type cytokine secretion than those of control groups. Wild PRV challenge experiment is performed using mice as a model animal, achieving a protection rate of up to 86.67 %, which is much higher than those observed from the commercial Alum. This work not only demonstrates the high potentiality of TPMnXC in practical applications but also provides a new way to develop the Mn 2+ -loaded nanoadjuvant for veterinary vaccines.
研究领域:
兽医学
·
免疫学
·
纳米技术
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-18
·
IF 14.7
Tang Xudong,Shang Yangyang,Yang Hong,Song Yalan,Li Shan,Qin Yusi,Song Jingyi,Chen Kang,Liu Yang,Zhang Dinglin,Chen Lei
The PD-1/PD-L1 pathway in mucosal immunity is currently actively explored and considered as a target for inflammatory bowel disease (IBD) treatment. However, systemic PD-L1 administration may cause unpredictable adverse effects due to immunosuppression. Here we show that reactive oxygen species (ROS)-responsive nanoparticles enhance the efficacy and safety of PD-L1 in a mouse colitis model. The nanoparticles control the accumulation and release of PD-L1 fused to Fc (PD-L1-Fc) at inflammatory sites in the colon. The nanotherapeutics shows superiority in alleviating inflammatory symptoms over systemic PD-L1-Fc administration and mitigates the adverse effects of PD-L1-Fc administration. The nanoparticles-formulated PD-L1-Fc affects production of proinflammatory and anti-inflammatory cytokines, attenuates the infiltration of macrophages, neutrophils, and dendritic cells, increases the frequencies of Treg, Th1 and Tfh cells, reshapes the gut microbiota composition; and increases short-chain fatty acid production. In summary, PD-L1-Fc-decorated nanoparticles may provide an effective and safe strategy for the targeted treatment of IBD.
研究领域:
药理学
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免疫学
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纳米技术
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Changcai Teng,Wenjing Ma,Jinfeng Liu,Juan Hou,Yalong Zhang,Xiongyan Meng,Yannan Xue,Zhen Wang,Jiajia Wang,Dexiang Chen,Qiang Sui,Qi Gao,Xia Li,Tiehai Li,Chengli Zong
Aberrantly glycosylated Mucin 1 (MUC1) is frequently over-expressed in epithelial cancers, making it an attractive target for cancer vaccines. Over the past two decades, multiple MUC1-based vaccines have been investigated clinically, yet they have generally shown limited efficacy due to challenges such as low immunogenicity, difficulty in overcoming immune tolerance, and potential issues related to glycosylation effects and antigen presentations. To advance the understanding of MUC1 vaccines, we report an efficient chemo-enzymatic approach for the preparation of four MUC1 antigen variants with different glycoforms through liquid-phase glycopeptide synthesis. These antigen were conjugated with CRM197 to generate various glycopeptide-protein conjugate vaccines, and their immunogenicity was evaluated based on total and subtype antibody titers, binding affinity, complement-dependent cytotoxicity (CDC) activity, and antibody-dependent cellular phagocytosis (ADCP). The combination of MPL and QS21 adjuvants with STn-MUC1-CRM197 conjugate induced a potent Th1-biased immune response, evidenced by elevating IgG2a titers and stronger antibody binding to MCF-7 cells. This formulation demonstrated superior CDC activity, ADCP activity and binding affinity to human breast cancer tissues in immuno-histochemical assays. The synergistic effect of specific adjuvants and glycosylated MUC1 conjugates offers a strategic avenue for MUC1 cancer vaccine development.
研究领域:
癌症研究
·
免疫学
·
化学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Zhihui Liang,Hang Bao,Zhiying Yao,Min Li,Chen Chen,Lei Zhang,Huiyang Wang,Yiyang Guo,Yubin Ma,Xuecheng Yang,Ge Yu,Jiancheng Zhang,Changying Xue,Bingbing Sun,Chuanbin Mao
In subunit vaccines, aluminum salts (Alum) are commonly used as adjuvants, but with limited cellular immune responses. To overcome this limitation, CpG oligodeoxynucleotides (ODNs) have been used in combination with Alum. However, current combined usage of Alum and CpG is limited to linear mixtures, and the underlying interaction mechanism between CpG and Alum is not well understood. Thus, we propose to chemically conjugate Alum nanoparticles and CpG (with 5′ or 3′ end exposed) to design combination adjuvants. Our study demonstrates that compared to the 3′-end exposure, the 5′-end exposure of CpG in combination adjuvants (Al-CpG-5′) enhances the activation of bone-marrow derived dendritic cells (BMDCs) and promotes Th1 and Th2 cytokine secretion. We used the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen (HBsAg) as model antigens to demonstrate that Al-CpG-5′ enhanced antigen-specific antibody production and upregulated cytotoxic T lymphocyte markers. Additionally, Al-CpG-5′ allows for coordinated adaptive immune responses even at lower doses of both CpG ODNs and HBsAg antigens, and enhances lymph node transport of antigens and activation of dendritic cells, promoting T fh cell differentiation and B cell activation. Our novel Alum-CPG strategy points the way towards broadening the use of nanoadjuvants for both prophylactic and therapeutic vaccines.
研究领域:
免疫学
·
纳米技术
·
疫苗学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Zhiting Cao,Jianye Ren,Yuguan Huang,Tong Li,Zhen Wang,Zhangyi Miao,Jia Jia,Yang Ding
Epidermal immunotherapy represents an emerging treatment method for allergic diseases. Nevertheless, an unformidable obstacle for epidermal drug delivery is the dense stratum corneum of the skin. Here, iontophoresis technology is utilized for epidermal delivery of allergen protein. Briefly, an iontophoresis patch consists of conductive nanofiber polypyrrole (PPy) and polyvinyl alcohol (PVA) by electrospinning technology, onto which cationic lipid dioctadecyl–dimethylammonium bromide vesicles containing ovalbumin (DDA@OVA) are loaded via electrospraying technology, forming a stable in situ composite structure. Compared with DDA@OVA/PVA, DDA@OVA/PPy-PVA demonstrated a significant increase in both allergen release and penetration into the epidermis. Ultimately, a high-level activation of antigen-presenting cells is facilitated. Importantly, DDA@OVA/PPy-PVA induces a significant increase in the levels of helper T cell 1 (Th1)-related cytokines such as IFN-γ and IL-12, inhibits the differentiation of T cells into Th2 cells, and further affects the secretion of OVA-specific IgE and promotes the production of protective antibody IgG. The lung tissue analysis illustrates that DDA@OVA/PPy-PVA treatment achieves regular alveolar structures in the lumen and significantly relieved asthma symptoms. The findings indicate that iontophoresis patches provide multiple benefits, including drug-responsive release, efficient penetration, and advanced therapeutic efficacy. These attributes make iontophoresis patches a promising treatment option for allergic diseases.
研究领域:
生物医学工程
·
药学
·
免疫学
·
过敏研究
·
药物递送系统
·
纳米技术
·
材料科学
·
呼吸系统疾病
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）