Biology-Basel
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2025
·Vol. 14
·期 5
·563
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IF 3.5
Lisha Ye,Simin Wu,Fuqiang Liu,Juan Zhang,Jie Wan,Chunqun Wang,Hui Liu,Min Hu
Simple SummaryHaemonchosis, caused byHaemonchus contortus, is a major parasitic disease in ruminants. The heavy reliance on anthelmintics has exacerbated drug resistance, making vaccine development imperative. H11 protein, a dominant antigen, confers partial immune protection to the host, but its formulation with the conventional QuilA adjuvant requires periodic booster immunizations. This study aimed to develop novel nano-adjuvants to enhance protective efficacy and prolong protection duration. Findings indicated that an immunostimulating complex matrix (IMX) combined with H11 protein elicited robust humoral immunity and durable immune memory in the host.The only vaccine againstHaemonchus contortusis limited by short-lived antibody persistence and the need for frequent booster immunizations. This study leveraged the advantages of nano-adjuvants in enhancing antigen presentation and immune regulation to evaluate the efficacy of novel adjuvants (IMX, AddaS03) and the conventional QuilA combined with H11 protein. Goats were divided into four groups (IMX + H11, AddaS03 + H11, QuilA + H11, and infected control). They were immunized three times and challenged with 6000 infective third-stage larvae (iL3s) ofH. contortuson the day of the third immunization, with the experiment lasting for 98 days. The results showed that vaccination with IMX + H11 conferred the strongest protection, demonstrating 88.3% efficacy in fecal egg count (FEC) reduction and 75.8% efficacy against worm burden, followed by QuilA + H11 (85.2% FEC reduction and 68% worm burden reduction) and AddaS03 + H11 (79.4% FEC reduction and 61.3% worm burden reduction). Serum IgG analysis revealed high antibody levels in all immunized groups. Cytokine detection found that IMX + H11 significantly upregulated IL-2 and IFN-γ expression in PBMCs and TNF-α expression in splenocytes, activating Th1-type responses and immune memory. QuilA + H11 showed weaker Th1 activation, and AddaS03 + H11 faced limitations due to insufficient antibody persistence for long-term protection. These findings suggest that IMX can induce highly efficient humoral and cellular immunity, providing a new direction for the optimization ofH. contortusvaccines and suggesting the importance of nano-adjuvants for precise regulation of immune patterns.
研究领域:
寄生虫学
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疫苗学
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Changmei Chen,Qinghua Yu,Lulu Wang,Rongchun Yi,Siying Huang,Xiangshu Cheng,Tao Deng
Chemotherapy combined with immunotherapy represents a promising combination therapy for tumor treatment. The low targeting of chemotherapeutic drugs and the potential immune-related adverse events (irAEs) of immune adjuvants hinder the realization of combination therapy. To solve these problems, we propose to further conjugate immunoadjuvant OVA using boric acid (BA) modified drug-carrying carbon dots, and develop a multifunctional nano drug delivery system for hierarchical targeting of focal sites (RCD@DOX/BA-O). From a mechanistic perspective, based on the pKa of BA, RCD@DOX/BA can couple OVA (1, 3-n-diol) under alkaline conditions and release OVA under tumor microenvironment, which could prevent the occurrence of irAEs. Furthermore, the exposed BA was able to combine with sialic acid (SA) (1, 2-n-diol) under the acidic tumor microenvironment, thereby enhancing its tumor-targeting capabilities. Specially, the immune effect (tumor-associated macrophages (TAMs) to M1) of OVA and the tumor targeted enhancement was verified by cell experiments. The treatment effect of RCD@DOX/BA-O was further proved on animal level. Overall, our finding suggests that the synthesized RCD@DOX/BA-O enabling synergistic chemotherapy and immunotherapy through hierarchical targeting to enhance anti-tumor efficacy and reduce irAEs. It is of great significance for targeted immunotherapy and improving the therapeutic effect of tumor.
研究领域:
纳米医学
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肿瘤学
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免疫学
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2011
·
IF 3.291
Tianyi Wang,Meijuan Zou,Haitao Jiang,Zhaoshuai Ji,Ping Gao,Gang Cheng
The purpose of this study is to develop a novel kind of adjuvant for oral vaccine delivery. In order to effectively prevent the degradation of antigens in the gastrointestinal tract and optimize the uptake for M cells, a novel kind of hydrophobic carbon nanoparticle (C1) with the size of 470 nm was synthesized by taking silica as a template and sucrose as a carbon source. Notably, there were large mesopores and macropores mainly of 40–60 nm, which made it to be excellent candidate as an antigen carrier. C1 was characterized using SEM, TEM and nitrogen adsorption. Following oral immunization with BSA loaded in C1, the IgG titer reached to a level almost equal to that of parenteral administration of antigen emulsified in Freund’s complete adjuvant (FCA). Mucosal IgA was also detected in intestinal, salivary and vaginal secretions, suggesting an effective stimulation of mucosal immune response. Besides, both T-helper 1 and T-helper 2 (Th1 or Th2) mediated responses were induced. We believe that the research will help in the design of novel vaccine adjuvant for improvement their potential on modulation of immune response.
研究领域:
生物医学工程
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免疫学
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产品关联
DOI
PubMed
高影响因子
ChemNanoMat
·
2024
·
IF 2.6
Yi Jiang,Chenglun Tang,Yilun Wu,Yishen Zhu
One of the main goals of present vaccine investigations is to develop a potent and efficient adjuvant strategy. The combination of multiple agonists to different pattern recognition receptor families offers great opportunities to achieve strong immune responses in a synergy manner. Here, we employed layered double hydroxide nanomaterials with BSA coating (LB) to integrate CpG and 3pRNA dual adjuvant cocktail, together with ovalbumin antigen. With LB loading, CpG and 3pRNA led to a quick internalization and enhanced induction of dendritic cell (DC) maturation. Meanwhile, this nanoadjuvant cocktail facilitated antigen crosspresenting in activated DCs. Taken together, these results may inspire the investigation of agonists combination and LDH-based nanoadjuvants.
研究领域:
免疫学
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纳米医学
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疫苗研究
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DOI
高影响因子
Materials Horizons
·
2025
·
IF 10.7
Yubo Liu,Fangming Liang,Rui Zhang,Chengcheng Tang,Xin Li,Yongjun Wang,Zhonggui He,Hongzhuo Liu
Recombinant adeno-associated virus (AAV) vectors have become the promising platform to deliver a therapeutic transgene for the treatment of monogenic disorders. However, anti-AAV antibodies that are released by B cells after AAV treatment create a substantial barrier to their long-lasting safe and effective therapy, making AAV gene therapy a “one shot” treatment. Here, we offered that tolerogenic nano-adjuvants (named RICP) composed of rapamycin (RAPA) and itaconate (ITA), to induce specific immune tolerance to overcome the anti-drug antibodies (ADAs). Such strategy blocked the feedback loops of follicular helper T （Tfh） cells and germinal center B cells by metabolic regulation, complementary to induction of regulatory T cells (Tregs) by mTORc1 inhibitor RAPA, consequently abolished the secretion of anti-AAV antibodies. The developed nano-adjuvants can also significantly increase expression of a transgene (such as luciferase, green fluorescent protein and human embryonic alkaline phosphatase reporter transgene) in the liver at re-dosing, compared to mice treated with AAV alone which showed almost no change in transgene expression. The emerging strategy provided AAV re-administration schedule available for not only mitigate toxicities with high vector doses, but re-storing therapeutic benefits in children in significant cell proliferation.
研究领域:
基因治疗
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免疫学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Nature Biomedical Engineering
·
2025
·
IF 26.6
Li Cuifeng,Li Yuxin,Zhou Bini,Li Tong,Wei Xiaohui,Chen Kun,Chen Wenlong,Shi Ziwei,Dai Xiaobin,Zhang Jiachen,Yang Chen,Ji Zhenglin,Sun Wenbo,Gao Ji,Wu Jing,Zhao Binbin,Min Xin,Li Yujie,Lin Lin,Yang Wei,Wang Min,Liu Zezhong,Liu Yaping,Zhu Chenyou,Yang Bo,Xu Jiang-Fei,Yan Li-Tang,Shi Yi,Lu Lu,Zhang Linqi,Ding Qiang,Xue Jing,Hou Baidong,Qi Hai,Liu Jiangning,Yang Yuhe R.,Liu Dongsheng,Liu Wanli
The emergence of novel infectious disease has intensified demand for more advanced vaccine development and more potent adjuvants to enhance immunogenicity. Here we introduce a dynamic DNA supramolecular matrix assembled from five unmodified, short DNA single strands, serving as a safe, multifaceted adjuvant platform. This DNA matrix elicits a robust humoral response with minimal adverse effects, generating potent neutralizing antibodies and conferring robust protection against SARS-CoV-2 and Streptococcus pneumoniae infections. Its dynamic colloidal feature prolongs the in vivo retention of both DNA and antigen, facilitating lymphatic-targeted transportation and presentation. This process leads to a robust pro-inflammatory response in both the vaccinated site and draining lymph node, which, in turn, promotes the recruitment and activation of immune cells, leading to a rapid, effective antigen-specific antibody response. The enhanced function of DNA matrix depends on the canonical TLR9–MyD88 signalling axis in dendritic cells. In addition, only right-handed, not left-handed, chirality of the DNA strands forms d -DNA matrix and promotes immune activations. Thus, this DNA matrix functions as an all-in-one adjuvant platform, opening promising avenues for future vaccine design.
研究领域:
免疫学
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微生物学
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生物材料
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疫苗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2020
·Vol. 7
·期 18
·2000771
·
IF 15.84
Tao Qin,Shang Ma,Xinyu Miao,Yan Tang,Dandan Huangfu,Jinyuan Wang,Jing Jiang,Nuo Xu,Yuncong Yin,Sujuan Chen,Xiufan Liu,Yinyan Yin,Daxin Peng,Lizeng Gao
Influenza poses a severe threat to global health. Despite the whole inactivated virus (WIV)-based nasal vaccine being a promising strategy for influenza protection, the mucosal barrier is still a bottleneck of the nasal vaccine. Here, a catalytic mucosal adjuvant strategy for an influenza WIV nasal vaccine based on chitosan (CS) functionalized iron oxide nanozyme (IONzyme) is developed. The results reveal that CS-IONzyme increases antigen adhesion to nasal mucosa by 30-fold compared to H1N1 WIV alone. Next, CS-IONzyme facilitates H1N1 WIV to enhance CCL20-driven submucosal dendritic cell (DC) recruitment and transepithelial dendrite(TED) formation for viral uptake via the toll-like receptor(TLR) 2/4-dependent pathway. Moreover, IONzyme with enhanced peroxidase (POD)-like activity by CS modification catalyzes a reactive oxygen species (ROS)-dependent DC maturation, which further enhances the migration of H1N1 WIV-loaded DCs into the draining lymph nodes for antigen presentation. Finally, CS-IONzyme-based nasal vaccine triggers an 8.9-fold increase of IgA-mucosal adaptive immunity in mice, which provides a 100% protection against influenza, while only a 30% protection by H1N1 WIV alone. This work provides an antiviral alternative for designing nasal vaccines based on IONzyme to combat influenza infection.
研究领域:
免疫学
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病毒学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Lisha Ye,Tianjiao Wang,Simin Wu,Hui Liu,Feng Liu,Chunqun Wang,Min Hu
The intestinal native protein H11 is one of the most immunodominant antigen of Haemonchus contortus . However, H11 combined with QuilA adjuvant shows only short-lived protection for animals. Nano-adjuvants have the huge potential to extend the immune response in human and animals. Here, we compared the immune responses induced by H11 combined with three nano-adjuvants including lipid nanoparticles (LNP), immunostimulating complex matrix (IMX) and AddaS03™. We measured the cytokine levels of goat PBMCs stimulated by H11 mixed with three nano-adjuvants and QuilA. Results showed that the transcriptions of IL-6, IL-8 and IFN-γ genes were significantly inhibited in all adjuvant group compared with PBS control. H11-IMX combination significantly up-regulated IL-2, IL-17 and TNF-α gene transcriptions. The H11-LNP group showed a significant increase in IL-17 and TNF-α transcriptions, while the H11-AddaS03™ group significantly increased IL-2 transcription. Additionally, mice immunized with these formulations were assessed for splenic lymphocyte proliferation. All H11-adjuvant combinations, except H11-LNP, significantly stimulated lymphocyte proliferation compared to the H11 alone and PBS control groups, with the H11-AddaS03™ combination showing the strongest effect. Analysis of serum antibody levels revealed that all immune groups induced high IgM levels, with H11-IMX inducing the highest IgG levels. Our results demonstrated that IMX or LNP combined with H11 mainly induced a Th17 cell immune response in goat PBMCs, while IMX or AddaS03™ combined with H11 could induce a strong humoral immune response in mice. This study elucidates the immune response profiles of different nano-adjuvant combined with H11 antigen, providing important insights for vaccine development against parasitic nematodes.
研究领域:
寄生虫学
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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
ACS Nano
·
2025
·
IF 16
Yan Deng,Hao Cheng,Ji Zhu,Yue Jiang,Hongwu Sun,Guocheng Li,Jing Wei,Ruoyi Xue,Rang Feng,Jingwen Cao,Wenkang Yu,Yalan Wang,Mingqi Xu,Quanming Zou,Haibo Li
Parenteral subunit vaccines typically elicit systemic humoral immune responses but often struggle to induce mucosal immunity. Herein, we developed a promising adjuvant system, TB/P2C-NE, a tamibarotene-loaded nanoemulsion incorporating the TLR2/6 agonist Pam2CSK4. Upon intramuscular vaccination, TB/P2C-NE promoted antigen-specific mucosal immune responses in the gastrointestinal tract, accompanied by systemic humoral and cellular response. Mechanistically, tamibarotene upregulated the intestinal homing molecule CCR9 on lymphocytes through dendritic cell modulation, while Pam2CSK4 increased IL-6 secretion at the injection sites, further amplifying CCR9 expression and lymphocyte activation and leading to enhanced lymphocyte homing to the intestinal mucosa and a subsequent boost in mucosal immunity. Notably, TB/P2C-NE induced long-term gastrointestinal mucosal responses, maintaining elevated sIgA levels for up to three months post-immunization, and also induced gastrointestinal mucosal immunity in combination with a polysaccharide conjugate antigen. Immunization with recombinant intimin using TB/P2C-NE as the adjuvant resulted in a robust protective effect against the EHEC O157:H7 challenge. In summary, TB/P2C-NE offers an adjuvant strategy potentially accelerating the development of vaccines targeting gastrointestinal infections.
研究领域:
免疫学
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疫苗学
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药剂学
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产品关联
DOI
PubMed
高影响因子
Nanomaterials
·
2022
·Vol. 12
·期 22
·3934
·
IF 5.719
Xiaoni Shi,Kun Yang,Hetao Song,Zhidong Teng,Yun Zhang,Weihao Ding,Aofei Wang,Shuzhen Tan,Hu Dong,Shiqi Sun,Yonghao Hu,Huichen Guo
The successful development of foot-and-mouth disease virus-like particles (FMD-VLPs) has opened a new direction for researching a novel subunit vaccine for foot-and-mouth disease (FMD). Therefore, it is urgent to develop an adjuvant that is highly effective and safe to facilitate a better immune response to be pair with the FMD-VLP vaccine. In this research, we prepared a new nano-emulsion adjuvant based on squalane (SNA) containing CpG using the pseudo-ternary phase diagram method and the phase transformation method. The SNA consisted of Span85, Tween60, squalane, polyethene glycol-400 (PEG400) and CpG aqueous solution. The average particle diameter of the SNA was about 95 nm, and it exhibited good resistance to centrifugation, thermal stability, and biocompatibility. Then, SNA was emulsified as an adjuvant to prepare foot-and-mouth disease virus-like particles vaccine,BALB/cmice and guinea pigs were immunized, and we evaluated the immunization effect. The immunization results in mice showed that the SNA-VLPs vaccine significantly increased specific antibody levels in mice within 4 weeks, including higher levels of IgG1 and IgG2a. In addition, it increased the levels of IFN-γ and IL-1β in the immune serum of mice. Meanwhile, guinea pig-specific and neutralizing antibodies were considerably increased within 4 weeks when SNA was used as an adjuvant, thereby facilitating the proliferation of splenic lymphocytes. More importantly, in guinea pigs immunized with one dose of SNA-VLPs, challenged with FMDV 28 days after immunization, the protection rate can reach 83.3%, which is as high as in the ISA-206 control group. In conclusion, the novel squalane nano-emulsion adjuvant is an effective adjuvant for the FMD-VLPs vaccine, indicating a promising adjuvant for the future development of a novel FMD-VLPs vaccine.Keywords:nano-emulsion;adjuvants;FMD virus-like particles;squalane;immune responses
研究领域:
病毒学
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免疫学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Bo Chen,Ruijie Huang,Wei Zeng,Wei Wang,Yuanzeng Min
The immunosuppressive tumor microenvironment (TME) greatly limits the actual outcome of immunotherapy. Therefore, it is urgent to develop appropriate strategies to reshape the TME and ultimately induce a strong immune response. Here, we developed a dual-functional liposome loaded with the photothermal agent IR808 near the infrared region (NIR) and Toll-like-receptor-7 (TLR7) agonist loxoribine prodrug (Lipo@IR808@Loxo) to achieve NIR light-triggered photothermal therapy (PTT) and the targeted delivery of immune adjuvants. Under NIR irradiation, Lipo@IR808@Loxo could greatly improve the efficiency of PTT to directly kill tumor cells and release tumor-associated antigens, which could work together with loaded loxoribine to relieve the immunosuppressive TME, effectively promoting the activation of antigen-presenting cells and subsequent antigen presentation . In this way, Lipo@IR808@Loxo could act as an in situ therapeutic cancer vaccine, eventually inducing a potent antitumor T-cell response. When further combined with immune checkpoint blockade, Lipo@IR808@Loxo-mediated photothermal immunotherapy could not only eliminate the primary tumors but also inhibit the growth of distant tumors, thus enhancing the abscopal effect.
研究领域:
肿瘤学
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免疫学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2025
·
IF 4.1
Meng-Ke Song,Meng-Qi Wang,Yu-Qing Ruan,Can Cui,Wen-Gang Chen,Opeyemi Joshua Olatunji,Yan Li,Jian Zuo
Introduction: Qing-Luo-Yin (QLY) is an anti-rheumatic herbal formula potentially activating PPARγ. The study investigated if and how this property contributes to its anti-angiogenesis effects.Methods: Adjuvant-induced arthritis (AIA) rats were orally treated by QLY or rosiglitazone (a PPARγ agonist), and their monocytes and lymphocytes were co-cultured reciprocally in vitro with different sera. Healthy littermates received blood transfusion from QLY-treated or AIA model rats. Two days ahead of sacrifice, a matrigel plug was implanted in the recipients. AIA serum-incubated THP-1 monocytes and Jurkat T cells were treated by a mixture comprised sinomenine, berberine and palmatine. Jurkat T cells-related media and T0070907 were used to stimulate human umbilical vein endothelial cells (HUVECs).Results: QLY and rosiglitazone similarly alleviated joint injuries, synovial angiogenesis and metabolic disorders in AIA rats. Although QLY impaired inflammatory phenotype of AIA rat monocytes in vivo, it cannot be achieved or sustained in vitro. Lymphocytes of QLY-treated AIA rats had a weak inflammatory phenotype and failed to induce inflammatory polarization of monocytes. AIA blood-induced angiogenesis in the matrigel plug, a phenomenon invisible in QLY group. QLY therapy inhibited pathogenic functions of AIA rats’ lymphocytes, shown by changes of cytokines network in the recipients’ joints, where these cells accumulated. The related compounds affected secretion of Jurkat T cells cultured in AIA serum, which lost the potential in activating HUVECs. This effect disappeared in presence of T0070907, a PPARγ inhibitor.Conclusion: Angiogenesis amelioration during QLY therapy is an indirect result from PPARγ activation-caused functional changes of T cells.
研究领域:
药理学
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免疫学
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风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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