VETERINARY RESEARCH
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2025
·Vol. 56
·期 1
·1-14
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IF 3.5
Li Peiyao,Su Rina,Ren Ganglin,Si Hongbin,Song Xingju,Hu Dandan
The apicomplexan parasite Eimeria is the causative agent of coccidiosis, which results in enteritis in animals and imposes a significant economic burden on the farming industry. Apicomplexan Apetala2/ERF (ApiAP2) transcription factors are known to play crucial roles in various processes of Apicomplexa parasites. However, little is understood regarding the role of ApiAP2s in Eimeria species. In this study, we performed a functional characterisation of ApiAP2 through CRISPR-Cas9-mediated knockout. Our results revealed that the parasite’s invasion efficiency, total oocyst output, and virulence were significantly impaired after EtAP2-S1 depletion. RNA sequencing (RNA-Seq) and Cleavage Under Targets and Tagmentation (CUT&Tag) analyses showed that EtAP2-S1 targets the promoters of numerous genes, and its knockout resulted in the up-regulation of 59 sag genes. Furthermore, the knockout strain exhibited significantly lower virulence while offering excellent immune protection, making it a promising candidate for a vaccine. This study demonstrates that EtAP2-S1 is a fitness-conferring gene that suppresses the expression of sag genes in E. tenella , which is the first step in developing gene-knockout vaccines to control coccidiosis.
研究领域:
分子生物学
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寄生虫学
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免疫学
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兽医学
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DOI
PubMed
高影响因子
Frontiers in Chemistry
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2022
·
IF 5.545
Xie Daping,Niu Yiming,Mu Ruoyu,Campos de Souza Senio,Yin Xiaoyu,Dong Lei,Wang Chunming
The global pandemic of COVID-19 highlights the importance of vaccination, which remains the most efficient measure against many diseases. Despite the progress in vaccine design, concerns with suboptimal antigen immunogenicity and delivery efficiency prevail. Self-adjuvant carriers–vehicles that can simultaneously deliver antigens and act as adjuvants–may improve efficacies in these aspects. Here, we developed a self-adjuvant carrier based on an acetyl glucomannan (acGM), which can activate toll-like receptor 2 (TLR2) and encapsulate the model antigen ovalbumin (OVA) via a double-emulsion process. In vitro tests showed that these OVA@acGM-8k nanoparticles (NPs) enhanced cellular uptake and activated TLR2 on the surface of dendritic cells (DCs), with increased expression of co-stimulatory molecules (e.g. CD80 and CD86) and pro-inflammatory cytokines (e.g. TNF-α and IL12p70). In vivo experiments in mice demonstrated that OVA@acGM-8k NPs accumulated in the lymph nodes and promoted DCs’ maturation. The immunization also boosted the humoral and cellular immune responses. Our findings suggest that this self-adjuvant polysaccharide carrier could be a promising approach for vaccine development.
研究领域:
免疫学
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纳米技术
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病毒学
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药学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2024
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IF 4.9
Mengxin Xu,Ying Liu,Huimin Chen,Weilun Hu,Yingying Li,Yuxin Zhang,Qingqing Wang,Tao Ma
s Vaccines play a crucial role in managing pandemic diseases like SARS and emerging coronaviruses. Efficient and quick detection methods for antigen-specific antibodies could significantly aid in designing vaccines intelligently. Presently, the detection of these antibodies typically involves the collection of blood and subsequent enzyme-linked immunosorbent assay, lateral flow immunoassay, and similar assay techniques. However, blood collection causes patient discomfort and pain, requiring professional handling and often resulting in poor patient compliance. This work is based on the establishment of a rapid vaccine antibody detection technique based on microneedle technology, in which microneedles modified with bio-recognition elements (such as antigens) penetrate the stratum corneum to extract interstitial fluid through capillary action and selectively capture protein biomarkers (such as antibodies) in the ISF in a concentration-dependent manner. The protein biomarkers attached to the microneedles are subsequently identified using an in vitro fluorescence immunoassay. This study merges the specificity inherent in antigen-antibody binding with the porous characteristics of microneedles to swiftly capture and detect antibodies within the skin's interstitial fluid. Compared to conventional testing methods, microneedle technology doesn't necessitate blood collection, rendering the technique non-invasive, minimally uncomfortable, and highly efficient. Moreover, it enables rapid antibody detection, offering a promising and straightforward approach to the efficient detection of various antibodies.
研究领域:
生物医学工程
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免疫学
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病毒学
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诊断医学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Jiabin Zhang,Kai Wang,Shiyao Xu,Linlin Chen,Haiquan Gu,Yujie Yang,Qi Zhao,Yurou Huo,Bo Li,Yufei Wang,Yubiao Xie,Nan Li,Jiali Zhang,Jianxu Zhang,Qianxue Li
Vaccines are widely regarded as one of the most effective weapons in the fight against infectious diseases. Currently, vaccines must be stored and transported at low temperatures as high temperatures can lead to a loss of vaccine conformation and reduced therapeutic efficacy. Metal–organic frameworks (MOFs), such as zeolitic imidazole framework-8 (ZIF-8), are a new class of hybrid materials with large specific surface areas, high loading rates, and good biocompatibility and are successful systems for vaccine delivery and protection. Silk fibroin (SF) has a good biocompatibility and thermal stability. In this study, the hepatitis B surface antigen (HBsAg) was successfully encapsulated in ZIF-8 to form HBsAg@ZIF-8 (HZ) using a one-step shake and one-pot shake method. Subsequently, the SF coating modifies HZ through hydrophobic interactions to form HBsAg/SF@ZIF-8 (HSZ), which enhanced the thermal stability and immunogenicity of HBsAg. Compared to free HBsAg, HZ and HSZ improved the thermostability of HBsAg, promoted the antigen uptake and lysosomal escape, stimulated dendritic cell maturation and cytokine secretion, formed an antigen reservoir to promote antibody production, and activated CD4+ T and CD8+ T cells to enhance memory T-cell production. Importantly, HSZ induced a strong immune response even after 14 days of storage at 25 °C. Furthermore, the nanoparticles prepared by the one-step shake method exhibited superior properties compared to those prepared by the one-pot shake method. This study highlights the importance of SF-coated ZIF-8, which holds promise for investigating thermostable vaccines and breaking the vaccine cold chain.
研究领域:
药学
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纳米技术
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免疫学
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疫苗开发
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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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
JOURNAL OF CONTROLLED RELEASE
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2024
·
IF 10.5
Ming Zhao,Chunting He,Xueyun Zheng,Min Jiang,Zhiqiang Xie,Hongjiao Wei,Shujun Zhang,Ying Lin,Jiaheng Zhang,Xun Sun
Vaccines represent one of the most powerful and cost-effective innovations for controlling a wide range of infectious diseases caused by various viruses and bacteria. Unlike mRNA and DNA-based vaccines, subunit vaccines carry no risk of insertional mutagenesis and can be lyophilized for convenient transportation and long-term storage. However, existing adjuvants are often associated with toxic effect and reactogenicity, necessitating expanding the repertoire of adjuvants with better biocompatibility, for instance, designing self-adjuvating polymeric carriers. We herein report a novel subunit vaccine delivery platform constructed via in situ free radical polymerization of C7A (2-(Hexamethyleneimino) ethyl methacrylate) and acrylamide around the surface of individual protein antigens. Using ovalbumin (OVA) as a model antigen, we observed substantial increases in both diameter (∼70 nm) and surface potential (−1.18 mV) following encapsulation, referred to as n( OVA )C7A. C7A's ultra pH sensitivity with a transition pH around 6.9 allows for rapid protonation in acidic environments. This property facilitates crucial processes such as endosomal escape and major histocompatibility complex (MHC)-I-mediated antigen presentation, culminating in the substantial CD8 + T cell activation. Additionally, compared to OVA nanocapsules without the C7A components and native OVA without modifications, we observed heightened B cell activation within the germinal center, along with remarkable increases in serum antibody and cytokine production. It's important to note that mounting evidence suggests that adjuvant effects, particularly its targeted stimulation of type I interferons (IFNs), can contribute to advantageous adaptive immune responses. Beyond its exceptional potency, the nanovaccine also demonstrated robust formation of immune memory and exhibited a favorable biosafety profile. These findings collectively underscore the promising potential of our nanovaccine in the realm of immunotherapy and vaccine development.
研究领域:
免疫学
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疫苗开发
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
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2024
·
IF 5.8
Zichao Huang,Zhenyi Zhu,Liping Liu,Wantong Song,Xuesi Chen
Virus-like nanoparticle vaccines can efficiently activate the humoral immune response by cross-linking B cell receptors with their surface multivalent antigen arrays. This structurally dependent mechanism makes it crucial to regulate and optimize structural parameters to enhance the efficacy of nanoparticle vaccines. In this study, we prepared nanoparticle vaccines with different aspect ratios by chemically modifying antigen proteins onto the surfaces of poly(amino acid) nanoparticles of various shapes (spherical, ellipsoidal, and rod-like). This allowed us to investigate the impact of structural anisotropy on the humoral immune activation efficacy of nanoparticle vaccines. Furthermore, the end-group molecules of poly(amino acid) materials possess aggregation-induced emission (AIE) properties, which facilitate monitoring the dynamics of nano-assemblies within the body. Results showed that rod-like nanoparticle vaccine (RLNVax) with higher aspect ratio (AR=5) exhibited greater lymph node draining efficiency and could elicit more effective B cell activation compared to conventional isotropic spherical nanoparticle vaccine. In a murine subcutaneous immunization model using ovalbumin (OVA) as a model antigen, RLNVax elicited antigen-specific antibody titers that were about 64 times and 4.6 times higher than those induced by free antigen protein and spherical nanoparticle vaccine, respectively. Additionally, when combined with aluminum adjuvant, antibody titers elicited by RLNVax were further enhanced by 4-fold. These findings indicate that the anisotropic rod-like structure is advantageous for improving the humoral immune activation efficacy of nanoparticle vaccines, providing significant insights for the design and optimization of next-generation nanoparticle vaccines.
研究领域:
纳米技术
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免疫学
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疫苗开发
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
·
IF 10
Hongping Wan,Kai Deng,Zhengqun Huang,Yunhan Yang,Bo Jing,Yumei Feng,Yuanfeng Li,Yong Liu,Mingqin Lu,Xinghong Zhao
Despite the safety profile of subunit vaccines, the inferior immunogenicity hinders their application in the nasal cavity. This study introduces a novel antigen delivery and adjuvant system utilizing mucoadhesive chitosan–catechol (Chic) on silica spiky nanoparticles (Ssp) to enhance immunity through multiple mechanisms. The Chic functionalizes the Ssp surface and incorporates with SARS-CoV-2 spike protein receptor-binding domain (RBD) and toll-like receptor (TLR)9 agonist unmethylated cytosine-guanine (CpG) motif, forming uniform virus-like nanoparticles (Ssp-Chic-RBD-CpG) via electrostatic and covalent interactions. Ssp-Chic-RBD-CpG, mimicking the morphology and function of inactive virions, effectively prolongs the retention time of RBD in the nasal mucosa by 3.92-fold compared to RBD alone, enhances the maturation of dendritic cells (DCs), and facilitates the antigen trafficking to the draining lymph nodes, which subsequently induces a stronger mucosal immunity. Mechanistically, the enhanced chemokine chemokine (C-C motif) ligand 20 (CCL20)-driven DCs recruitment and maturation by Ssp-Chic-RBD-CpG are evidenced by a cell co-culture model. In addition, the overexpression of TLR4/9 and activation of MYD88/NF-κB signaling pathway in activation of DCs are observed. Proof of principle is obtained for RBD, but similar delivery mechanisms can be applied in other protein-based subunit vaccines as well when intranasal administration is needed.
研究领域:
纳米技术
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免疫学
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疫苗开发
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分子生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2024
·
IF 15.8
Zijin Luo,Yi Lin,Yanan Meng,Mengyao Li,Hongyu Ren,Haoping Shi,Qiang Cheng,Tuo Wei
The successful application of mRNA vaccines in preventing and treating infectious diseases highlights their potential as therapeutic vaccines for cancer treatment. However, unlike infectious diseases, effective antitumor therapy, particularly for solid tumors, necessitates the activation of more powerful cellular and humoral immunity to achieve clinical efficacy. Here, we report a spleen-targeted mRNA vaccine (Mn@mRNA-LNP) designed to deliver tumor antigen-encoding mRNA and manganese adjuvant (Mn2+) simultaneously to dendritic cells (DCs) in the spleen. This delivery system promotes DC maturation and surface antigen presentation and stimulates the production of cytotoxic T cells. Additionally, Mn2+ codelivered in the system serves as a safe and effective immune adjuvant, activating the stimulator of interferon genes (STING) signaling pathway and promoting the secretion of type I interferon, further enhancing the antigen-specific T cell responses. Mn@mRNA-LNP effectively inhibits tumor progression in established melanoma and colon tumor models as well as in a model of tumor recurrence after resection. Notably, the combination of Mn@mRNA-LNP with immune checkpoint inhibitors further enhances complete tumor suppression and prolonged the overall survival in mice. Overall, this “All-in-One” mRNA vaccine significantly boosts antitumor immunity responses by improving spleen targeting and immune activation, providing an attractive strategy for the future clinical translation of therapeutic mRNA vaccines.
研究领域:
癌症免疫治疗
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疫苗开发
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR THERAPY
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2025
·
IF 12
Jingjing Zhang,Chao Li,Yuheng Liu,Rui Liao,Dian He,Lifeng Xu,Tingting Chen,Qin Xiao,Mingxing Luo,Yang Chen,Yali Li,Huaxing Zhu,Joseph Rosenecker,Xiaoyan Ding,Shuchen Pei,Shan Guan
The development of mucosal mRNA vaccines is promising but extremely challenging. Major efforts have been focused on optimizing delivery systems, whereas it is still unknown whether the intrinsic quality of mRNA components significantly impacts the potency of airway inoculated mRNA vaccines. Here, we systematically demonstrate mucosal mRNA vaccine requires higher standards of purification and tailor-designed sequence to fulfil its potency compared to parenteral-route inoculated counterpart. Double-stranded RNA (dsRNA) contaminants are prone to trigger innate immune response in the airway that activates the mRNA degradation mechanism, thereby diminishing the mRNA expression and subsequent antigen-specific immune responses. To address these challenges, we developed a strategy that combines optimized untranslated regions (UTRs) screened from endogenous genes of pulmonary cells with affinity chromatography-based purification which effectively removed dsRNA contaminants. The optimized mRNA administered via airway route not only demonstrated superior protein expression (30-fold increase) and reduced inflammation in the lung, but also promoted robust immunity comprising significantly elevated systemic, cellular, and mucosal immune responses, which was in stark contrast to intramuscular injected counterpart that displays less pronounced benefits. Our findings offer new insights into the development of mucosal mRNA therapeutics from an overlooked but crucial perspective of optimizing mRNA components.
研究领域:
免疫学
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分子生物学
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疫苗开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
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2024
·
IF 5.7
Lu Chenhe,Li Haimin,Chen Wenjing,Li Hui,Ma Jiayu,Peng Peng,Yan Yan,Dong Weiren,Jin Yulan,Pan Shiyue,Shang Shaobin,Gu Jinyan,Zhou Jiyong
Introduction: Variant pseudorabies virus (PRV) is a newly emerged zoonotic pathogen that can cause human blindness. PRV can take advantage of its large genome and multiple non-essential genes to construct recombinant attenuated vaccines carrying foreign genes. However, a major problem is that the foreign genes in recombinant PRV are only integrated into the genome for independent expression, rather than assembled on the surface of virion.Methods: We reported a recombinant PRV with deleted gE/TK genes and an inserted porcine circovirus virus 2 (PCV2) Cap gene into the extracellular domain of the PRV gE gene using the Cre-loxP recombinant system combined with the CRISPR-Cas9 gene editing system. This recombinant PRV (PRV-Cap), with the envelope-embedded Cap protein, exhibits a similar replication ability to its parental virus.Results: An immunogenicity assay revealed that PRV-Cap immunized mice have 100% resistance to lethal PRV and PCV2 attacks. Neutralization antibody and ELISPOT detections indicated that PRV-Cap can enhance neutralizing antibodies to PRV and produce IFN-γ secreting T cells specific for both PRV and PCV2. Immunological mechanistic investigation revealed that initial immunization with PRV-Cap stimulates significantly early activation and expansion of CD69+ T cells, promoting the activation of CD4 Tfh cell dependent germinal B cells and producing effectively specific effector memory T and B cells. Booster immunization with PRV-Cap recalled the activation of PRV-specific IFN-γ+IL-2+CD4+ T cells and IFN-γ+TNF-α+CD8+ T cells, as well as PCV2-specific IFN-γ+TNF-α+CD8+ T cells.Conclusion: Collectively, our data suggested an immunological mechanism in that the recombinant PRV with envelope-assembled PCV2 Cap protein can serve as an excellent vaccine candidate for combined immunity against PRV and PCV2, and provided a cost-effective method for the production of PRV- PCV2 vaccine.
研究领域:
病毒学
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免疫学
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分子生物学
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疫苗开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Zheng Jia,Xinyao Zhou,Jingjing Liu,Xinqi De,Yifan Li,Zaixing Yang,Haoyuan Duan,Fang Wang,Junwei Ge
The use of biomimetic mineralization strategy is promising to solve the problem of poor stability and immune effect of subunit antigens. However, non-specifically inducing protein mineralization is still a challenge. we hypothesized that rhamnolipids with both protein and metal binding capacity could be used to develop more functional and biocompatible calcium mineralized nanoparticle (RMCP). The results show that rhamnolipids synergistically enhanced the mineralization of protein with manganese ions and improved 21 % the loading antigens of RMCP compared to manganese calcium phosphate nanoparticles. Transmission electron microscopy (TEM) and Dynamic Light Scattering (DLS) showed particle size of RMCP is 260 ± 12.1 nm with spherical morphology. In vitro experiments have shown that RMCP effectively activate immune cells through the cGAS-STING and NLRP3 pathways and demonstrated a higher level of cytokines in RAW264.7 Macrophages. In vivo, RMCP triggered an increased IgG titer with 16.5-fold IgG2a/IgG1 ratio compared to the aluminum adjuvant which improved the recovery status after challenge in mice. We used biological surfactants for the first time to enhance the biomimetic mineralization process of subunit antigen, which provides a new approach for constructing calcium-based biocompatible antigen delivery vectors, helping to develop a new generation of stable, efficient, and safe subunit vaccines.
研究领域:
免疫学
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纳米技术
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疫苗开发
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生物材料
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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）