nanovaccines

纳米疫苗
  • 文章类型: Journal Article
    已经设计了纳米疫苗以克服与常规疫苗相关的限制。有效的递送方法如工程载体或智能纳米颗粒(NPs)是诱导自我耐受性和优化疫苗免疫原性且副作用最小的关键必要条件。NP可以用作佐剂,免疫原,或纳米载体以开发用于有效抗原递送的纳米疫苗。携带多种肿瘤抗原和免疫刺激剂的多载纳米疫苗可以有效地增加对肿瘤细胞的免疫力。它们可以被生物工程化以增强与树突细胞的相互作用并允许逐渐和恒定的抗原释放。修改NP表面属性,使用高密度脂蛋白模拟纳米盘,以及开发基于纳米的人工抗原呈递细胞,如树突状细胞衍生的外泌体,是增强针对肿瘤细胞的抗原呈递和免疫反应的新开发技术之一。本综述概述了不同的观点,改进,以及当前癌症治疗和疫苗接种方案成功临床应用的障碍。描述了不同类型的纳米疫苗和掺入其结构中的纳米颗粒的免疫调节作用。使用纳米疫苗预防和治疗艾滋病等常见疾病的优势,疟疾,讨论了癌症和结核病。Further,描述了开发最佳癌症疫苗的潜在途径。鉴于癌细胞和肿瘤微环境的免疫抑制特性,免疫调节剂和免疫检查点抑制剂与其他常规抗癌疗法联合应用对于提高免疫反应的有效性是必要的.
    Nanovaccines have been designed to overcome the limitations associated with conventional vaccines. Effective delivery methods such as engineered carriers or smart nanoparticles (NPs) are critical requisites for inducing self-tolerance and optimizing vaccine immunogenicity with minimum side effects. NPs can be used as adjuvants, immunogens, or nanocarriers to develop nanovaccines for efficient antigen delivery. Multiloaded nanovaccines carrying multiple tumor antigens along with immunostimulants can effectively increase immunity against tumor cells. They can be biologically engineered to boost interactions with dendritic cells and to allow a gradual and constant antigen release. Modifying NPs surface properties, using high-density lipoprotein-mimicking nanodiscs, and developing nano-based artificial antigen-presenting cells such as dendritic cell-derived-exosomes are amongst the new developed technologies to enhance antigen-presentation and immune reactions against tumor cells. The present review provides an overview on the different perspectives, improvements, and barriers of successful clinical application of current cancer therapeutic and vaccination options. The immunomodulatory effects of different types of nanovaccines and the nanoparticles incorporated into their structure are described. The advantages of using nanovaccines to prevent and treat common illnesses such as AIDS, malaria, cancer and tuberculosis are discussed. Further, potential paths to develop optimal cancer vaccines are described. Given the immunosuppressive characteristics of both cancer cells and the tumor microenvironment, applying immunomodulators and immune checkpoint inhibitors in combination with other conventional anticancer therapies are necessary to boost the effectiveness of the immune response.
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  • 文章类型: Journal Article
    长期以来,卵巢癌(OC)的死亡率一直是妇科恶性肿瘤中最高的。虽然OC被认为是一种免疫原性肿瘤,免疫治疗效果不理想。免疫抑制微环境是其中一个原因,另一个原因是缺乏公认的疫苗有效抗原。化疗,作为OC最常用的治疗方法之一,在治疗过程中可以产生化疗相关抗原(CAAs),并显示出原位疫苗的效果。在这里,我们设计了一种抗原捕获纳米疫苗NP-TP1@M-M,其肿瘤靶向肽TMTP1和树突状细胞(DC)受体甘露糖组装在表面,佐剂单磷酰脂质A(MPLA)包裹在聚(D,L-丙交酯-共-乙交酯)(PLGA)纳米颗粒。PLGA本身具有抗原捕获能力。TMTP1是由我们的研究小组筛选的肿瘤归巢肽,具有广泛而优异的肿瘤靶向能力。经过这些修改,NP-TP1@M-M可以在化疗后捕获和富集更多的肿瘤特异性抗原,刺激DC成熟,激活适应性免疫,并结合免疫检查点封锁,以最大限度地释放身体的免疫潜能,为OC的治疗提供了一种良好的治疗策略。
    The mortality of ovarian cancer (OC) has long been the highest among gynecological malignancies. Although OC is considered to be an immunogenic tumor, the effect of immunotherapy is not satisfactory. The immunosuppressive microenvironment is one reason for this, and the absence of recognized effective antigens for vaccines is another. Chemotherapy, as one of the most commonly used treatment for OC, can produce chemotherapy-associated antigens (CAAs) during treatment and show the effect of in situ vaccine. Herein, we designed an antigen capture nano-vaccine NP-TP1@M-M with tumor targeting peptide TMTP1 and dendritic cell (DC) receptor mannose assembled on the surface and adjuvant monophosphoryl lipid A (MPLA) encapsulated in the core of poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA itself possessed the ability of antigen capture. TMTP1 was a tumor-homing peptide screened by our research team, which held extensive and excellent tumor targeting ability. After these modifications, NP-TP1@M-M could capture and enrich more tumor-specific antigens after chemotherapy, stimulate DC maturation, activate the adaptive immunity and combined with immune checkpoint blockade to maximize the release of the body\'s immune potential, providing an eutherapeutic strategy for the treatment of OC.
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  • 文章类型: Journal Article
    纳米疫苗治疗是免疫学和个性化医学研究的一个令人兴奋的领域,在增强免疫反应和针对特定疾病方面有着巨大的希望。它们的小尺寸允许免疫细胞有效吸收,导致强大的免疫激活。它们可以掺入免疫刺激分子以提高疫苗效力。因此,纳米疫苗可以个性化靶向肿瘤特异性抗原,激活免疫系统对抗癌细胞。目前,有充分的证据表明纳米疫苗作为癌症治疗的有效性和潜力。然而,有罕见的癌症纳米疫苗的文献计量学分析。在这里,我们对已发表的与纳米疫苗治疗癌症相关的研究进行了文献计量和视觉分析,未来纳米疫苗的发展趋势。
    我们收集了基于WebofScienceCoreCollectionSCI扩展数据库的文献。文献计量分析是通过利用可视化分析工具VOSviewer进行的,共同发生(COOC),城市空间,Bibliometrix(R-ToolofR-Studio),还有Hitcite.
    本研究共纳入517篇文献。中国是出版物最多的国家,也是当地引文总分(TLCS)最高的国家。中国科学院拥有该领域最大的研究数量,最多产的作者是南开大学的德令孔。该领域最著名的期刊是生物材料。研究主要集中在肿瘤纳米疫苗的治疗过程,纳米疫苗的颗粒组成和应用,提示纳米疫苗的潜在热点和趋势。
    在这项研究中,我们总结了涉及纳米疫苗的出版物的特征和变化趋势,并对最具影响力的国家进行了分类,机构,作者,期刊,关于癌症纳米疫苗的热点和趋势。随着纳米材料和肿瘤免疫治疗技术的不断发展,纳米疫苗为癌症提供了一个具有重要临床价值和潜在应用的研究领域。
    UNASSIGNED: Nanovaccine treatment is an exciting area of research in immunology and personalized medicine, holding great promise for enhancing immune responses and targeting specific diseases. Their small size allows efficient uptake by immune cells, leading to robust immune activation. They can incorporate immune-stimulating molecules to boost vaccine efficacy. Therefore, nanovaccine can be personalized to target tumor-specific antigens, activating the immune system against cancer cells. Currently, there have been ample evidence showing the effectiveness and potential of nanovaccine as a treatment for cancer. However, there was rare bibliometric analysis of nanovaccine for cancer. Here we performed a bibliometric and visual analysis of published studies related to nanovaccine treatment for cancer, providing the trend of future development of nanovaccine.
    UNASSIGNED: We collected the literatures based on the Web of Science Core Collection SCI-Expanded database. The bibliometric analysis was performed via utilizing visualization analysis tools VOSviewer, Co-Occurrence (COOC), Citespace, Bibliometrix (R-Tool of R-Studio), and HitCite.
    UNASSIGNED: A total of 517 literatures were included in this study. China is the country with the most publications and the highest total local citation score (TLCS). The Chinese Academy of Sciences holds the largest research count in this field and the most prolific author is Deling Kong from Nankai University. The most prominent journal for publishing in this area is Biomaterials. The researches mainly focus on the therapeutic process of tumor nanovaccines, the particle composition and the application of nanovaccines, suggesting the potential hotspots and trends of nanovaccine.
    UNASSIGNED: In this study, we summarized the characteristics and variation trends of publications involved in nanovaccine, and categorized the most influential countries, institutions, authors, journals, hotspots and trends regarding the nanovaccine for cancer. With the continuous development of nanomaterials and tumor immunotherapy, nanovaccine for cancer provides a research field of significant clinical value and potential application.
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  • 文章类型: Journal Article
    首批批准的人类使用的针对严重急性呼吸道综合症冠状病毒2(SARS-CoV-2)的疫苗是基于纳米技术的。虽然它们是模块化的,迅速生产,可以减轻疾病的严重程度,目前可用的疫苗在预防感染方面受到限制,强调全球对新型预防性疫苗技术的需求。记住这一点,我们着手开发一种灵活的纳米疫苗平台,用于鼻腔给药以诱导粘膜免疫,这是防止呼吸道病毒感染的最佳保护的基础。下一代多表位纳米疫苗共同递送免疫原性肽,通过免疫信息学工作流程选择,以及PD-L1表达的佐剂和调节剂。作为一个案例研究,我们以SARS-CoV-2肽作为相关抗原来验证该方法。该平台可以引起针对SARS-CoV-2的局部和系统性细胞和体液特异性反应。这导致免疫球蛋白A(IgA)的分泌,能够中和SARS-CoV-2,包括关注的变种,遵循异源免疫策略。考虑到当前基于纳米技术的疫苗所需的冷链分布的局限性,这表明冻干的纳米疫苗在室温下是长期稳定的,并且在重建时保持其体内功效。这使其与发展中国家特别相关,并提供了适应未来病毒威胁的模块化系统。
    The first approved vaccines for human use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are nanotechnology-based. Although they are modular, rapidly produced, and can reduce disease severity, the currently available vaccines are restricted in preventing infection, stressing the global demand for novel preventive vaccine technologies. Bearing this in mind, we set out to develop a flexible nanovaccine platform for nasal administration to induce mucosal immunity, which is fundamental for optimal protection against respiratory virus infection. The next-generation multiepitope nanovaccines co-deliver immunogenic peptides, selected by an immunoinformatic workflow, along with adjuvants and regulators of the PD-L1 expression. As a case study, we focused on SARS-CoV-2 peptides as relevant antigens to validate the approach. This platform can evoke both local and systemic cellular- and humoral-specific responses against SARS-CoV-2. This led to the secretion of immunoglobulin A (IgA), capable of neutralizing SARS-CoV-2, including variants of concern, following a heterologous immunization strategy. Considering the limitations of the required cold chain distribution for current nanotechnology-based vaccines, it is shown that the lyophilized nanovaccine is stable for long-term at room temperature and retains its in vivo efficacy upon reconstitution. This makes it particularly relevant for developing countries and offers a modular system adaptable to future viral threats.
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  • 文章类型: Journal Article
    带状疱疹(HZ),也被称为带状疱疹,仍然是一个重要的全球健康问题,最常见于有水痘-带状疱疹病毒(VZV)早期接触史的老年人。目前,许可的疫苗Shingrix,它包含与强效佐剂AS01B配制的重组VZV糖蛋白E(gE),是市场上最有效的带状疱疹疫苗。然而,不希望的反应原性和全球需求的增加导致疫苗短缺,促使新型带状疱疹疫苗的开发。这里,我们开发了新的候选疫苗利用多个纳米颗粒(NP)平台来展示重组gE抗原,在MF59生物仿制药佐剂中配制。在幼稚的小鼠中,所有测试的NP疫苗都比Shingrix诱导更高的体液和细胞免疫反应,其中,gEM候选者诱导最高的细胞反应。在活减毒VZV(VZVLAV)引发的小鼠和恒河猴模型中,gEM候选物引起优于Shingrix的细胞介导免疫(CMI)。总的来说,我们证明了NP技术仍然是开发带状疱疹疫苗的合适工具,报道的gEM构建体是下一代带状疱疹疫苗开发中非常有希望的候选者。
    Herpes zoster (HZ), also known as shingles, remains a significant global health issue and most commonly seen in elderly individuals with an early exposure history to varicella-zoster virus (VZV). Currently, the licensed vaccine Shingrix, which comprises a recombinant VZV glycoprotein E (gE) formulated with a potent adjuvant AS01B, is the most effective shingles vaccine on the market. However, undesired reactogenicity and increasing global demand causing vaccine shortage, prompting the development of novel shingles vaccines. Here, we developed novel vaccine candidates utilising multiple nanoparticle (NP) platforms to display the recombinant gE antigen, formulated in an MF59-biosimilar adjuvant. In naïve mice, all tested NP vaccines induced higher humoral and cellular immune responses than Shingrix, among which, the gEM candidate induced the highest cellular response. In live attenuated VZV (VZV LAV)-primed mouse and rhesus macaque models, the gEM candidate elicited superior cell-mediated immunity (CMI) over Shingrix. Collectively, we demonstrated that NP technology remains a suitable tool for developing shingles vaccine, and the reported gEM construct is a highly promising candidate in the next-generation shingles vaccine development.
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  • 文章类型: Journal Article
    SenecavirusA(SVA)是一种可引起猪水泡病的病原体,这对世界养猪业造成了极大的威胁。因此,有必要开发一种可以有效防止SVA传播的疫苗。在这项研究中,我们使用来自番茄丛生效应病毒(TBSV)的β-环肽通过将该抗原与SVAB细胞表位VP121-26和VP2蛋白通过接头偶联,开发了一种24聚合纳米支架,分别。通过低成本原核系统表达和纯化VP1(B)-β-VP2的基于SVA的纳米颗粒蛋白以制备SVA纳米颗粒疫苗。在小鼠和猪模型中评估SVA纳米颗粒疫苗的免疫保护作用。分别。结果表明,小鼠和猪在两次免疫后均可诱导高水平的SVA中和抗体和IgG抗体。此外,猪攻击保护实验表明,免疫SVA纳米颗粒疫苗和SVA灭活疫苗的保护率均为80%,阴性对照无保护作用。证明SVA纳米颗粒疫苗能有效预防猪SVA感染。总之,利用β-环肽制备SVA疫苗是一种有前途的预防SVA传播的候选疫苗,为新型SVA疫苗的研制提供了新的思路。
    Senecavirus A (SVA) is a causative agent that can cause vesicular disease in swine, which causes a great threat to the swine husbandry in the world. Therefore, it is necessary to develop a vaccine that can effectively prevent the spread of SVA. In this study, we developed a 24-polymeric nano-scaffold using β-annulus peptide from tomato bushy effect virus (TBSV) by coupling this antigen to SVA B cell epitope VP121-26 and VP2 proteins via linkers, respectively. The SVA-based nanoparticle protein of the VP1(B)-β-VP2 was expressed and purified by low-cost prokaryotic system to prepare a SVA nanoparticle vaccine. The immunological protective effect of SVA nanoparticle vaccine was evaluated in mouse and swine models, respectively. The results suggested that both mice and swine could induce high levels SVA neutralizing antibodies and IgG antibodies after two doses immunization. In addition, the swine challenge protection experiment showed that the protection rate of immune SVA nanoparticle vaccine and SVA inactivated vaccine both were 80 %, while the negative control had no protection effect. It demonstrated that SVA nanoparticle vaccine effectively prevented SVA infection in swine. In summary, the preparation of SVA vaccine by using β-annulus peptide is a promising candidate vaccine for prevent SVA transmission, and provides a new idea for the development of novel SVA vaccines.
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  • 文章类型: Journal Article
    由SARS-CoV-2产生的COVID-19已经严重影响了全球的医疗保健系统。这一流行病凸显了疫苗开发的迫切需要。除了传统的疫苗接种模型,其中包括活减毒,重组蛋白,和灭活疫苗,纳米疫苗为推进疫苗研究和提供方便的替代品提供了一个独特的机会。这篇综述重点介绍了许多广泛使用的纳米颗粒疫苗载体,概述了它们的优点和缺点,并研究了预防SARS-CoV-2的纳米颗粒疫苗的最新进展。它还全面概述了纳米颗粒疫苗的许多优点,包括增强的宿主免疫反应,多价抗原递送,和有效的药物输送。主要目的是为创新抗病毒疫苗的开发提供参考。
    COVID-19, generated by SARS-CoV-2, has significantly affected healthcare systems worldwide. The epidemic has highlighted the urgent need for vaccine development. Besides the conventional vaccination models, which include live-attenuated, recombinant protein, and inactivated vaccines, nanovaccines present a distinct opportunity to progress vaccine research and offer convenient alternatives. This review highlights the many widely used nanoparticle vaccine vectors, outlines their benefits and drawbacks, and examines recent developments in nanoparticle vaccines to prevent SARS-CoV-2. It also offers a thorough overview of the many advantages of nanoparticle vaccines, including an enhanced host immune response, multivalent antigen delivery, and efficient drug delivery. The main objective is to provide a reference for the development of innovative antiviral vaccines.
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  • 文章类型: Journal Article
    加强流感疫苗交叉保护是减轻流感重大公共卫生负担的当务之急。异源序贯免疫可以协同多种疫苗制剂和途径以提高疫苗效力和广度。在这里,我们研究了免疫策略对雌性Balb/c小鼠产生交叉保护性免疫应答的影响,利用针对流感血凝素的mRNA脂质纳米颗粒(LNP)和基于蛋白质的PHC纳米颗粒疫苗。我们的发现强调了启动疫苗接种在塑造Th偏见和免疫优势等级中的关键作用。mRNALNP主要有利于Th1倾向反应,而PHC素数引发Th2偏斜反应。我们证明,细胞和粘膜免疫反应是抗流感交叉保护的关键相关因素。值得注意的是,鼻内PHC免疫在诱导粘膜免疫和赋予交叉保护方面优于其肌内对应物。顺序的mRNALNP引发和鼻内PHC加强显示针对抗原漂移和转移的流感毒株的最佳交叉保护。我们的研究为定制免疫策略以优化流感疫苗的有效性提供了有价值的见解。
    Enhancing influenza vaccine cross-protection is imperative to alleviate the significant public health burden of influenza. Heterologous sequential immunization may synergize diverse vaccine formulations and routes to improve vaccine potency and breadth. Here we investigate the effects of immunization strategies on the generation of cross-protective immune responses in female Balb/c mice, utilizing mRNA lipid nanoparticle (LNP) and protein-based PHC nanoparticle vaccines targeting influenza hemagglutinin. Our findings emphasize the crucial role of priming vaccination in shaping Th bias and immunodominance hierarchies. mRNA LNP prime favors Th1-leaning responses, while PHC prime elicits Th2-skewing responses. We demonstrate that cellular and mucosal immune responses are pivotal correlates of cross-protection against influenza. Notably, intranasal PHC immunization outperforms its intramuscular counterpart in inducing mucosal immunity and conferring cross-protection. Sequential mRNA LNP prime and intranasal PHC boost demonstrate optimal cross-protection against antigenically drifted and shifted influenza strains. Our study offers valuable insights into tailoring immunization strategies to optimize influenza vaccine effectiveness.
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  • 文章类型: Journal Article
    SARS-CoV-2疫苗的快速发展已用于预防2019年冠状病毒(COVID-19)的传播。然而,由SARS-CoV-2变异体和突变引起的持续和未来的大流行凸显了对提供广谱保护的有效疫苗的需求.这里,我们开发了一种纳米颗粒疫苗,对不同的SARS-CoV-2变种具有广泛的保护作用.将预先存在的中和(CePn)抗体的相应保守表位呈递在自组装幽门螺杆菌铁蛋白上以产生CePnF纳米颗粒。CePnF纳米粒诱导小鼠经鼻免疫,细胞,粘膜免疫反应和持久的免疫力。CePnF诱导的抗体表现出针对不同冠状病毒(CoV)的交叉反应性和中和活性。接种CePnF显著抑制SARS-CoV-2Delta的复制和病理,HACE2转基因小鼠中的WIV04和Omicron菌株,因此,对这些SARS-CoV-2变体具有广泛的保护作用。我们构建的针对预先存在的中和抗体的保守表位的纳米疫苗可以作为通用SARS-CoV-2疫苗的有希望的候选者。
    The rapid development of the SARS-CoV-2 vaccine has been used to prevent the spread of coronavirus 2019 (COVID-19). However, the ongoing and future pandemics caused by SARS-CoV-2 variants and mutations underscore the need for effective vaccines that provide broad-spectrum protection. Here, we developed a nanoparticle vaccine with broad protection against divergent SARS-CoV-2 variants. The corresponding conserved epitopes of the preexisting neutralizing (CePn) antibody were presented on a self-assembling Helicobacter pylori ferritin to generate the CePnF nanoparticle. Intranasal immunization of mice with CePnF nanoparticles induced robust humoral, cellular, and mucosal immune responses and a long-lasting immunity. The CePnF-induced antibodies exhibited cross-reactivity and neutralizing activity against different coronaviruses (CoVs). CePnF vaccination significantly inhibited the replication and pathology of SARS-CoV-2 Delta, WIV04, and Omicron strains in hACE2 transgenic mice and, thus, conferred broad protection against these SARS-CoV-2 variants. Our constructed nanovaccine targeting the conserved epitopes of the preexisting neutralizing antibodies can serve as a promising candidate for a universal SARS-CoV-2 vaccine.
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  • 文章类型: Journal Article
    猪繁殖与呼吸综合征病毒(PRRSV)对全球养猪业构成重大威胁。开发高效亚单位纳米疫苗是预防PRRSV变异体感染的有希望的策略。在这项研究中,针对主要糖蛋白GP5的两种不同类型的铁蛋白(Ft)纳米疫苗,分别称为GP5m-Ft和(Bp-IVp)3-Ft,构建并评估为PRRSV的候选疫苗。透射电子显微镜(TEM)和动态光散射(DLS)表明,纯化的GP5m-Ft和(Bp-IVp)3-Ft蛋白都可以自组装成纳米球。在BALB/c小鼠中,用灭活的PRRSV疫苗比较GP5m-Ft和(Bp-IVp)3-Ft的免疫原性表明,用GP5m-Ft免疫的小鼠表现出最高的ELISA抗体水平,中和抗体滴度,淋巴细胞增殖指数,和IFN-γ水平。此外,接种GP5m-Ft纳米颗粒可有效保护仔猪免受高致病性PRRSV攻击。这些发现表明GP5m-Ft是控制PRRS的有希望的候选疫苗。
    Porcine reproductive and respiratory syndrome virus (PRRSV) presents a significant threat to the global swine industry. The development of highly effective subunit nanovaccines is a promising strategy for preventing PRRSV variant infections. In this study, two different types of ferritin (Ft) nanovaccines targeting the major glycoprotein GP5, named GP5m-Ft and (Bp-IVp)3-Ft, were constructed and evaluated as vaccine candidates for PRRSV. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) demonstrated that both purified GP5m-Ft and (Bp-IVp)3-Ft proteins could self-assemble into nanospheres. A comparison of the immunogenicity of GP5m-Ft and (Bp-IVp)3-Ft with an inactivated PRRSV vaccine in BALB/c mice revealed that mice immunized with GP5m-Ft exhibited the highest ELISA antibody levels, neutralizing antibody titers, the lymphocyte proliferation index, and IFN-γ levels. Furthermore, vaccination with the GP5m-Ft nanoparticle effectively protected piglets against a highly pathogenic PRRSV challenge. These findings suggest that GP5m-Ft is a promising vaccine candidate for controlling PRRS.
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