vaccine delivery

疫苗递送
  • 文章类型: Journal Article
    治疗性癌症疫苗是FDA批准的首批癌症免疫疗法之一。其中,它仍然是一个主要的挑战,以实现强大的淋巴结(LN)积累。然而,由于淋巴管的独特结构,将货物运送到LN是困难的,和临床反应在很大程度上令人失望。在这里,受从外围到LN的迁移DC归巢的启发,描述了一种可注射的基于水凝胶的多肽疫苗系统,用于增强免疫刺激功效,这可能会在DC上形成疫苗的局部利基“搭便车”。由水凝胶中的亲脂性DSPE结构域修饰的OVA肽自发地插入细胞膜中以在体内实现DC上的“抗原锚定”。总的来说,OVA肽通过招募和“搭便车”皮下迁移DC来实现主动访问LN。值得注意的是,已证明,与游离OVA肽相比,复合水凝胶将LN靶向功效增强约6倍。然后,OVA肽可以在LN内典型的酸性微环境下从细胞表面去除,通过“一对多”策略(一个迁移DC对应于许多LN驻留APC)进一步与LN驻留APC共享它们,从而激活强大的免疫刺激。此外,所述水凝胶疫苗在黑素瘤中表现出显著的肿瘤生长抑制并抑制肺转移性结节形成。
    Therapeutic cancer vaccines are among the first FDA-approved cancer immunotherapies. Among them, it remains a major challenge to achieve robust lymph-node (LN) accumulation. However, delivering cargo into LN is difficult owing to the unique structure of the lymphatics, and clinical responses have been largely disappointing. Herein, inspired by the Migrated-DCs homing from the periphery to the LNs, an injectable hydrogel-based polypeptide vaccine system is described for enhancing immunostimulatory efficacy, which could form a local niche of vaccine \"hitchhiking\" on DCs. The OVA peptide modified by lipophilic DSPE domains in the hydrogel is spontaneously inserted into the cell membrane to achieve \"antigen anchoring\" on DCs in vivo. Overall, OVA peptide achieves active access LNs through recruiting and \"hitchhiking\" subcutaneous Migrated-DCs. Remarkably, it is demonstrated that the composite hydrogel enhances LNs targeting efficacy by approximately six-fold compared to free OVA peptide. Then, OVA peptide can be removed from the cell surface under a typical acidic microenvironment within the LNs, further share them with LN-resident APCs via the \"One-to-Many\" strategy (One Migrated-DC corresponding to Many LN-resident APCs), thereby activating powerful immune stimulation. Moreover, the hydrogel vaccine exhibits significant tumor growth inhibition in melanoma and inhibits pulmonary metastatic nodule formation.
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  • 文章类型: Journal Article
    目的:本研究旨在评估真空包装中表达针对大肠癌的K-ras(克里斯汀大鼠肉瘤病毒癌基因同源物)模拟表位的冻干重组乳酸乳球菌NZ3900发酵奶粉的储存稳定性。
    结果:在整个49天的加速储存(38°C和90%相对湿度)中评价储存在4层可蒸煮聚丙烯(RCPP)-聚酰胺(PA)-铝(AL)-聚对苯二甲酸乙二醇酯(PET)和铝聚乙烯(ALPE)中的冻干乳酸乳球菌发酵奶粉。储存在4层包装中的发酵奶粉保持高于6log10CFUg-1的活力,水分含量较低(6.1%),更高的流动性(43°静止角),水溶性(62%),和乳酸乳球菌在模拟胃和肠消化后的存活率(>82%)比ALPE包装在42天的加速储存后。储存后,在冻干乳酸乳球菌发酵奶粉的细胞内和细胞外检测到K-ras模拟表位表达。
    结论:这表明发酵奶粉是这种口服活疫苗的合适食品载体。
    OBJECTIVE: This study aims to evaluate the storage stability of the freeze-dried recombinant Lactococcus lactis NZ3900-fermented milk powder expressing K-ras (Kristen rat sarcoma viral oncogene homolog) mimotopes targeting colorectal cancer in vacuum packaging.
    RESULTS: The freeze-dried L. lactis-fermented milk powder stored in 4-ply retortable polypropylene (RCPP)-polyamide (PA)-aluminium (AL)-polyethylene terephthalate (PET) and aluminium polyethylene (ALPE) was evaluated throughout 49 days of accelerated storage (38°C and 90% relative humidity). The fermented milk powder stored in 4-ply packaging remained above 6 log10 CFU g-1 viability, displayed lower moisture content (6.1%), higher flowability (43° angle of repose), water solubility (62%), and survivability of L. lactis after simulated gastric and intestinal digestion (>82%) than ALPE packaging after 42 days of accelerated storage. K-ras mimotope expression was detected intracellularly and extracellularly in the freeze-dried L. lactis-fermented milk powder upon storage.
    CONCLUSIONS: This suggests that fermented milk powder is a suitable food carrier for this live oral vaccine.
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  • 文章类型: Journal Article
    养猪已成为全球具有战略意义和经济重要性的行业。由于跨界疾病所带来的挑战,它也是一个潜在的脆弱部门,病毒感染是最重要的。在猪病毒性疾病中,非洲猪瘟,经典猪瘟,口蹄疫,猪繁殖与呼吸综合征,伪狂犬病,猪流感,传染性胃肠炎是一些在养猪业造成重大经济损失的疾病。众所周知,疫苗接种无疑是控制动物病毒感染的最有效策略。从詹纳和巴斯德时期到最近的新一代技术时代,疫苗的开发大大有助于减轻病毒感染对动物和人类的负担。灭活和修饰的活病毒疫苗提供针对关键病原体的部分保护。然而,有必要改进这些疫苗,以更全面地应对新出现的感染,并确保其安全性。最近关于针对DNA等猪病毒的新一代疫苗的报道,基于病毒载体的复制子,嵌合,肽,植物制造,病毒样粒子,基于纳米粒子的疫苗非常令人鼓舞。当前的评论收集了有关可用疫苗的全面信息以及对猪病毒疫苗的未来展望。
    Pig farming has become a strategically significant and economically important industry across the globe. It is also a potentially vulnerable sector due to challenges posed by transboundary diseases in which viral infections are at the forefront. Among the porcine viral diseases, African swine fever, classical swine fever, foot and mouth disease, porcine reproductive and respiratory syndrome, pseudorabies, swine influenza, and transmissible gastroenteritis are some of the diseases that cause substantial economic losses in the pig industry. It is a well-established fact that vaccination is undoubtedly the most effective strategy to control viral infections in animals. From the period of Jenner and Pasteur to the recent new-generation technology era, the development of vaccines has contributed significantly to reducing the burden of viral infections on animals and humans. Inactivated and modified live viral vaccines provide partial protection against key pathogens. However, there is a need to improve these vaccines to address emerging infections more comprehensively and ensure their safety. The recent reports on new-generation vaccines against swine viruses like DNA, viral-vector-based replicon, chimeric, peptide, plant-made, virus-like particle, and nanoparticle-based vaccines are very encouraging. The current review gathers comprehensive information on the available vaccines and the future perspectives on porcine viral vaccines.
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  • 文章类型: Journal Article
    社区参与对于以人为本的发展至关重要,成功的疫苗接种计划。多样化的疫苗接种接受研究网络(VARN)社区汇集了来自整个免疫生态系统的跨学科专业人士,他们在疫苗接种接受中发挥着至关重要的作用。需求,和交付。在VARN2023会议的过程中,研究人员和从业人员都分享了想法和经验,重点是在社区和卫生系统之间建立信任以增加疫苗接种公平性的战略和方法。卫生专业人员和社区成员必须在设计和提供以社区为中心的免疫服务方面具有同等价值,虽然主要疫苗接种决策者也必须考虑社区经验,关注,以及方案设计和决策方面的专业知识。因此,社区参与和培养社区信任的策略对于任何免疫计划的成功至关重要。此外,卫生工作者需要额外的技能,支持,和资源来有效地传达有关免疫的复杂信息,包括打击错误信息的有效策略。本文总结了VARN2023会议上提供的三个技能建设会议,专注于以人为本的设计,动机性面试,并与记者接触以利用社区的声音。这些会议提供了实用的,可供从业者使用的跨地理和社会环境使用的基于证据的工具,研究人员,和其他利益相关者,以增加其社区的疫苗接种需求和吸收。
    Community engagement is vital to the development of people-centered, successful vaccination programs. The diverse Vaccination Acceptance Research Network (VARN) community brings together interdisciplinary professionals from across the immunization ecosystem who play a crucial role in vaccination acceptance, demand, and delivery. Over the course of the VARN2023 conference, researchers and practitioners alike shared ideas and experiences focused on strategies and approaches to building trust between communities and health systems to increase equity in vaccination. Health professionals and community members must have equal value in the design and delivery of community-centered immunization services, while key vaccination decision-makers must also consider community experiences, concerns, and expertise in program design and policymaking. Therefore, strategies for community engagement and cultivating trust with communities are crucial for the success of any immunization program. Furthermore, health workers need additional skills, support, and resources to effectively communicate complex information about immunization, including effective strategies for countering misinformation. This article summarizes three skills-building sessions offered at the VARN2023 conference, focused on human-centered design, motivational interviewing, and engaging with journalists to leverage the voices of communities. These sessions offered practical, evidence-based tools for use across geographic and social settings that can be used by practitioners, researchers, and other stakeholders to increase vaccination demand and uptake in their communities.
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  • 文章类型: Journal Article
    脂质囊泡已广泛用于药物和基因递送,但它们的结构不稳定性降低了体内功效,需要专门处理运输和储存。为了解决这些限制,已经提出了诸如脂质交联和聚合物-脂质缀合的策略来增强囊泡稳定性并改善生物学功效。然而,体内代谢的化学变化的脂质仍不清楚,促使需要对其实际应用进行广泛的研究。因此,迫切需要一种无需化学改性的新稳定技术。这里,我们提出了一种生物模拟方法来制造强大的多层脂质囊泡,这大大增强了蛋白质抗原的体内递送和稳定性。我们的新方法利用1-O-酰基神经酰胺,天然存在于皮肤中的脂质,以促进脂质纳米囊泡的自组装。掺入1-O-酰基神经酰胺,锚定脂质双层的作用类似于它在角质层中的作用,在环境压力下赋予多层囊泡优异的稳定性,包括反复的冻融循环。卵清蛋白作为模型抗原和佐剂单磷酰脂质A的封装证明了杂合囊泡作为纳米疫苗平台的潜力。体外细胞研究表明,单层和多层囊泡都能增强免疫反应,但是在体内分析中,多层囊泡在诱导更高水平的抗体和细胞因子分泌方面明显更有效。这项工作表明神经酰胺诱导的多层脂质囊泡作为有效的纳米疫苗平台,有希望的增强抗原递送和稳定性,以改善体内抗原交叉呈递。本文受版权保护。保留所有权利。
    Lipid vesicles are widely used for drug and gene delivery, but their structural instability reduces in vivo efficacy and requires specialized handling. To address these limitations, strategies like lipid cross-linking and polymer-lipid conjugation are suggested to enhance stability and biological efficacy. However, the in vivo metabolism of these altered lipids remains unclear, necessitating further studies. A new stabilization technique without chemical modification is urgently needed. Here, a bio-mimetic approach for fabricating robust multilamellar lipid vesicles to enhance in vivo delivery and stabilization of protein antigens is presented. This method leverages 1-O-acylceramide, a natural skin lipid, to facilitate the self-assembly of lipid nanovesicles. Incorporating 1-O-acylceramide, anchoring lipid bilayers akin to its role in the stratum corneum, provides excellent stability under environmental stresses, including freeze-thaw cycles. Encapsulating ovalbumin as a model antigen and the adjuvant monophosphoryl lipid A demonstrates the vesicle\'s potential as a nanovaccine platform. In vitro studies show enhanced immune responses with both unilamellar and multilamellar vesicles, but in vivo analyses highlight the superior efficiency of multilamellar vesicles in inducing higher antibody and cytokine levels. This work suggests ceramide-induced multilamellar lipid vesicles as an effective nanovaccine platform for enhanced antigen delivery and stability.
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  • 文章类型: Journal Article
    疫苗的递送在影响免疫应答的强度和寿命以及控制反应原性方面起着关键作用。粘膜免疫,与肠胃外疫苗接种相比,可以提供更好的保护,防止呼吸道感染,同时具有较小的侵入性。虽然口服疫苗被认为效果较差,并被认为主要针对胃肠道,使用粘膜粘附膜(MAF)的经颊递送可允许靶向递送至粘膜。在这里,我们提出了一种有效的策略,用于粘膜递送纳入MAF的几种疫苗平台,包括DNA质粒,病毒载体,和掺入mRNA(mRNA/LNP)的脂质纳米颗粒。作为概念证明的针对SARS-CoV-2的mRNA/LNP疫苗制剂在由缓慢释放的水溶性聚合物和不可渗透的背衬层组成的MAF中保持稳定。促进增强渗透到口腔粘膜。该制剂引起与肌内注射相当的抗体和细胞反应。但也诱导粘膜IgA的产生,突出其功效,特别是用作加强疫苗和预防呼吸道感染的潜在优势。MAF疫苗制剂显示出显著的优势,如高效交付,稳定性,和简单的非侵入性给药,有可能减轻疫苗的犹豫。
    The delivery of vaccines plays a pivotal role in influencing the strength and longevity of the immune response and controlling reactogenicity. Mucosal immunization, as compared to parenteral vaccination, could offer greater protection against respiratory infections while being less invasive. While oral vaccination has been presumed less effective and believed to target mainly the gastrointestinal tract, trans-buccal delivery using mucoadhesive films (MAF) may allow targeted delivery to the mucosa. Here we present an effective strategy for mucosal delivery of several vaccine platforms incorporated in MAF, including DNA plasmids, viral vectors, and lipid nanoparticles incorporating mRNA (mRNA/LNP). The mRNA/LNP vaccine formulation targeting SARS-CoV-2 as a proof of concept remained stable within MAF consisting of slowly releasing water-soluble polymers and an impermeable backing layer, facilitating enhanced penetration into the oral mucosa. This formulation elicited antibody and cellular responses comparable to the intramuscular injection, but also induced the production of mucosal IgAs, highlighting its efficacy, particularly for use as a booster vaccine and the potential advantage for protection against respiratory infections. The MAF vaccine preparation demonstrates significant advantages, such as efficient delivery, stability, and simple noninvasive administration with the potential to alleviate vaccine hesitancy.
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  • 文章类型: Journal Article
    随着Onco免疫疗法(OIMT)的引入,癌症治疗取得了重大进展。尽管其中一些疗法已获得批准使用,其他人要么正在进行测试,要么仍处于开发的早期阶段。在使免疫疗法广泛适用于癌症治疗方面仍然存在挑战。为了最大限度地发挥免疫疗法的益处并最大限度地减少潜在的副作用,提高不同免疫疗法的反应率至关重要。该领域的有希望的发展是使用细胞外囊泡(EV)作为新型递送系统。这些小囊泡可以有效地提供免疫疗法,增强其有效性并减少有害副作用。本文讨论了将纳米药物整合到OIMT中的重要性,突出了当前反OIMT方法的挑战。它还探讨了设计为OIMT定制的纳米药物的关键考虑因素,旨在改进现有的免疫治疗技术。此外,这篇文章探讨了创新的方法,如生物模拟和使用天然生物材料基纳米载体(NC)。这些进步有可能改变免疫疗法的递送。最后,本文讨论了将OIMT从理论转移到临床实践的挑战,提供在癌症治疗中使用先进的纳米技术的未来见解。
    Cancer treatment has seen significant advancements with the introduction of Onco-immunotherapies (OIMTs). Although some of these therapies have received approval for use, others are either undergoing testing or are still in the early stages of development. Challenges persist in making immunotherapy widely applicable to cancer treatment. To maximize the benefits of immunotherapy and minimize potential side effects, it\'s essential to improve response rates across different immunotherapy methods. A promising development in this area is the use of extracellular vesicles (EVs) as novel delivery systems. These small vesicles can effectively deliver immunotherapies, enhancing their effectiveness and reducing harmful side effects. This article discusses the importance of integrating nanomedicines into OIMTs, highlighting the challenges with current anti-OIMT methods. It also explores key considerations for designing nanomedicines tailored for OIMTs, aiming to improve upon existing immunotherapy techniques. Additionally, the article looks into innovative approaches like biomimicry and the use of natural biomaterial-based nanocarriers (NCs). These advancements have the potential to transform the delivery of immunotherapy. Lastly, the article addresses the challenges of moving OIMTs from theory to clinical practice, providing insights into the future of using advanced nanotechnology in cancer treatment.
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  • 文章类型: Journal Article
    疫苗学中的纳米制剂提供抗原稳定性和增强的免疫原性,除了提供靶向递送和控制释放。在过去的几年里,许多研究都集中在使用病毒样颗粒的疫苗开发上,脂质体,乳液,聚合物,脂质,和无机纳米粒子。重要的是,必须清楚地了解纳米粒子与先天和适应性免疫系统的相互作用,以指导纳米疫苗的合理发展。这篇综述提供了关于倡导纳米粒子作为有前途的抗原载体和免疫细胞激活剂用于疫苗接种的不同方面的回顾和更新。此外,它讨论了如何修饰纳米粒子的物理化学性质以靶向特定细胞并提高疫苗效力。
    Nanoformulations in vaccinology provide antigen stability and enhanced immunogenicity, in addition to providing targeted delivery and controlled release. In the last years, much research has been focused on vaccine development using virus-like particles, liposomes, emulsions, polymeric, lipid, and inorganic nanoparticles. Importantly, nanoparticle interactions with innate and adaptive immune systems must be clearly understood to guide the rational development of nanovaccines. This review provides a recap and updates on different aspects advocating nanoparticles as promising antigen carriers and immune cell activators for vaccination. Moreover, it offers a discussion of how the physicochemical properties of nanoparticles are modified to target specific cells and improve vaccine efficacy.
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  • 文章类型: Journal Article
    近年来,肿瘤疫苗被认为是治疗癌症的有希望的治疗方法。随着测序技术的发展,基于肿瘤细胞中特异性表达的新抗原或基因组的肿瘤疫苗,主要是肽的形式,核酸,和树突状细胞,开始受到广泛关注。因此,在这次审查中,我们介绍了不同形式的新抗原疫苗,并讨论了这些疫苗在治疗癌症方面的发展。此外,新抗原疫苗受抗原稳定性等因素的影响,弱免疫原性,和生物安全除了测序技术。因此,生物纳米材料,聚合物纳米材料,无机纳米材料,等。,用作疫苗载体的主要概述,这可能有助于新抗原疫苗的设计,以提高稳定性和更好的功效。
    Tumor vaccines have been considered a promising therapeutic approach for treating cancer in recent years. With the development of sequencing technologies, tumor vaccines based on neoantigens or genomes specifically expressed in tumor cells, mainly in the form of peptides, nucleic acids, and dendritic cells, are beginning to receive widespread attention. Therefore, in this review, we have introduced different forms of neoantigen vaccines and discussed the development of these vaccines in treating cancer. Furthermore, neoantigen vaccines are influenced by factors such as antigen stability, weak immunogenicity, and biosafety in addition to sequencing technology. Hence, the biological nanomaterials, polymeric nanomaterials, inorganic nanomaterials, etc., used as vaccine carriers are principally summarized here, which may contribute to the design of neoantigen vaccines for improved stability and better efficacy.
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  • 文章类型: Journal Article
    In December 2021 the U.S. Government announced a new, whole-of-government $1.8 billion effort, the Initiative for Global Vaccine Access (Global VAX) in response to the global COVID-19 pandemic. Using the foundation of decades of U.S. government investments in global health and working in close partnership with local governments and key global and multilateral organizations, Global VAX enabled the rapid acceleration of the global COVID-19 vaccine rollout in selected countries, contributing to increased COVID-19 vaccine coverage in some of the world\'s most vulnerable communities. Through Global VAX, the U.S. Government has supported 125 countries to scale up COVID-19 vaccine delivery and administration while strengthening primary health care systems to respond to future health crises. The progress made by Global VAX has paved the way for a stronger global recovery and improved global health security.
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