nanovaccine

纳米疫苗
  • 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
    传染性鼻炎(IC)是由Avibacterium引起的鸡的急性上呼吸道疾病(A.)副细菌。这种疾病导致肉鸡的剔除率增加,产蛋和繁殖母鸡的产蛋量显着下降(10%至40%以上)。疫苗首先用于预防IC,并有效控制了疾病。纳米技术为开发新一代疫苗提供了极好的途径。NP已广泛用于疫苗设计中,作为佐剂和抗原递送载体以及作为抗菌剂;因此,它们可以用作细菌培养的灭活剂。在这项研究中,几种纳米粒子(NPs)的抗菌作用,如二氧化硅与壳聚糖(SiO2-CS),油酰基-壳聚糖(O.CS),二氧化硅(SiO2),和氧化铁(Fe3O4),对A.paragallinarum进行了研究。此外,使用相同的纳米材料以400µg/ml的浓度制备不同的副鸡副鸡A.所测试的所有NP的400μg/ml的浓度是灭活副鸡曲霉的最佳浓度。此外,这项研究表明,以SiO2NPs为佐剂的传染性Coryza疫苗具有最高的免疫应答,其次是用Fe3O4NP佐剂的传染性鼻炎疫苗,以SiO2-CSNP为佐剂的传染性鼻炎疫苗,与用液体石蜡(一种商业疫苗)佐剂的传染性coryza疫苗相比,用O.CSNP佐剂的传染性coryza疫苗。
    Infectious coryza (IC) is an acute upper respiratory disease of chicken caused by Avibacterium (A.) paragallinarum. This disease results in an increased culling rate in meat chicken and a marked decrease in egg production (10% to more than 40%) in laying and breeding hens. Vaccines were first used against IC and effectively controlled the disease. Nanotechnology provides an excellent way to develop a new generation of vaccines. NPs have been widely used in vaccine design as adjuvants and antigen delivery vehicles and as antibacterial agents; thus, they can be used as inactivators for bacterial culture. In this research, the antibacterial effects of several nanoparticles (NPs), such as silicon dioxide with chitosan (SiO2-CS), oleoyl-chitosan (O.CS), silicon dioxide (SiO2), and iron oxide (Fe3O4), on A. paragallinarum were studied. Additionally, different A. paragallinarum vaccines were made using the same nanomaterials at a concentration of 400 µg/ml to help control infectious coryza disease in chicken. A concentration of 400 µg/ml of all the NPs tested was the best concentration for the inactivation of A. paragallinarum. Additionally, this study showed that the infectious coryza vaccine adjuvanted with SiO2 NPs had the highest immune response, followed by the infectious coryza vaccine adjuvanted with Fe3O4 NPs, the infectious coryza vaccine adjuvanted with SiO2-CS NPs, and the infectious coryza vaccine adjuvanted with O.CS NPs in comparison with the infectious coryza vaccine adjuvanted with liquid paraffin (a commercial vaccine).
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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
    需要安全有效的候选疫苗来解决现有针对布鲁氏菌病的疫苗的局限性,一种对牲畜造成重大经济损失的疾病。本研究旨在封装Omp25和EipB蛋白,公认的抗原特性,变成PLGA纳米粒子,用不同的方法表征合成的纳米颗粒,并评估其体外/体内免疫刺激活性以开发新的候选疫苗。通过双乳液溶剂蒸发技术将重组DNA技术产生的rOmp25和EipB蛋白包封到PLGA纳米颗粒中。使用SEM对纳米粒子进行了表征,Zeta-sizer,和FTIR仪器来确定尺寸,形态学,zeta电位,和多分散指数值,以及化学分析官能团。此外,使用UV-Vis光谱法评估释放曲线和包封效率.装载重组蛋白后,O-NP的大小达到221.2±5.21nm,而E-NP的大小达到274.4±9.51nm。抗原的累积释放速率,监测至第14天结束,确定O-NP为90.39%,E-NP为56.1%。在评估蛋白质和纳米颗粒对J774鼠巨噬细胞的体外细胞毒性和免疫刺激作用后,使用每种蛋白质的浓度为16μg/ml进行体内免疫实验。与对照相比,游离抗原和含抗原的纳米颗粒均通过将产生的布鲁氏菌特异性IgG抗体水平提高3倍来过度诱导体液免疫。此外,还证明了疫苗候选物也刺激了Th1介导的细胞免疫,因为它们在免疫后显著提高了小鼠脾细胞中IFN-γ和IL-12细胞因子水平,而不是IL-4.此外,根据攻击结果,候选疫苗对感染的保护超过90%.我们的发现表明,用重组Omp25或EipB蛋白封装构建的PLGA纳米颗粒具有触发布鲁氏菌特异性体液和细胞免疫应答的巨大潜力。
    Safe and effective vaccine candidates are needed to address the limitations of existing vaccines against Brucellosis, a disease responsible for substantial economic losses in livestock. The present study aimed to encapsulate recombinant Omp25 and EipB proteins, knowledged antigen properties, into PLGA nanoparticles, characterize synthesized nanoparticles with different methods, and assessed theirin vitro/in vivoimmunostimulatory activities to develop new vaccine candidates. The recombinant Omp25 and EipB proteins produced with recombinant DNA technology were encapsulated into PLGA nanoparticles by double emulsion solvent evaporation technique. The nanoparticles were characterized using FE-SEM, Zeta-sizer, and FT-IR instruments to determine size, morphology, zeta potentials, and polydispersity index values, as well as to analyze functional groups chemically. Additionally, the release profiles and encapsulation efficiencies were assessed using UV-Vis spectroscopy. After loading with recombinant proteins, O-NPs reached sizes of 221.2 ± 5.21 nm, while E-NPs reached sizes of 274.4 ± 9.51 nm. The cumulative release rates of the antigens, monitored until the end of day 14, were determined to be 90.39% for O-NPs and 56.1% for E-NPs. Following the assessment of thein vitrocytotoxicity and immunostimulatory effects of both proteins and nanoparticles on the J774 murine macrophage cells,in vivoimmunization experiments were conducted using concentrations of 16µg ml-1for each protein. Both free antigens and antigen-containing nanoparticles excessively induced humoral immunity by increasing producedBrucella-specific IgG antibody levels for 3 times in contrast to control. Furthermore, it was also demonstrated that vaccine candidates stimulated Th1-mediated cellular immunity as well since they significantly raised IFN-gamma and IL-12 cytokine levels in murine splenocytes rather than IL-4 following to immunization. Additionally, the vaccine candidates conferred higher than 90% protection from the infection according to challenge results. Our findings reveal that PLGA nanoparticles constructed with the encapsulation of recombinant Omp25 or EipB proteins possess great potential to triggerBrucella-specific humoral and cellular immune response.
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  • 文章类型: Journal Article
    嗜水气单胞菌,一种机会性的温水病原体,一直是水产养殖的威胁,造成了巨大的经济损失。对养殖鱼类进行疫苗接种将有效预防气单胞菌病,纳米技术的最新进展显示了有效疫苗的前景。口服递送将是在长大的池塘中最实用和最方便的疫苗递送方法。这项研究研究了斑马鱼模型中来自嗜水蛋白A的纳米颗粒负载的外膜蛋白A的免疫原性和保护功效。蛋白质过度表达,纯化,并通过双乳液法使用聚乳酸-羟基乙酸共聚物(PLGA)纳米颗粒包封。负载有重组OmpA(rOmpA)的PLGA纳米颗粒表现出295±15.1nm的尺寸,封装效率为72.52%,多分散指数为0.292±0.07。扫描电子显微镜证实了PLGA-rOmpA纳米颗粒的球形和分离性质。在口服施用纳米疫苗后,嗜水气单胞菌感染的斑马鱼的保护效力导致77.7的相对存活百分比。基因表达研究表明,接种疫苗的鱼中免疫基因的显着上调。结果表明,口服装载纳米疫苗的rOmpA作为潜在的疫苗是有用的,因为它诱导了强大的免疫反应,并在斑马鱼中提供了针对嗜水气单胞菌的足够保护。DanioRerio.
    Aeromonas hydrophila, an opportunistic warm water pathogen, has always been a threat to aquaculture, leading to substantial economic losses. Vaccination of the cultured fish would effectively prevent Aeromoniasis, and recent advancements in nanotechnology show promise for efficacious vaccines. Oral delivery would be the most practical and convenient method of vaccine delivery in a grow-out pond. This study studied the immunogenicity and protective efficacy of a nanoparticle-loaded outer membrane protein A from A. hydrophila in the zebrafish model. The protein was over-expressed, purified, and encapsulated using poly lactic-co-glycolic acid (PLGA) nanoparticles via the double emulsion method. The PLGA nanoparticles loaded with recombinant OmpA (rOmpA) exhibited a size of 295 ± 15.1 nm, an encapsulation efficiency of 72.52%, and a polydispersity index of 0.292 ± 0.07. Scanning electron microscopy confirmed the spherical and isolated nature of the PLGA-rOmpA nanoparticles. The protective efficacy in A. hydrophila-infected zebrafish after oral administration of the nanovaccine resulted in relative percentage survival of 77.7. Gene expression studies showed significant upregulation of immune genes in the vaccinated fish. The results demonstrate the usefulness of oral administration of nanovaccine-loaded rOmpA as a potential vaccine since it induced a robust immune response and conferred adequate protection against A. hydrophila in zebrafish, Danio rerio.
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  • 文章类型: Journal Article
    基于猪的完整病毒或刺突蛋白,δ冠状病毒(PDCoV)作为免疫原可能具有无关的抗原表位干扰。因此,它对于筛选和鉴定有利的保护性抗原表位是必不可少的。此外,免疫信息学工具被描述为确定保护性抗原表位的重要辅助手段。在这项研究中,主要的,次要,使用ExPASy测量疫苗的三级结构,PSIPRED4.0和trRosetta服务器。同时,构建了候选纳米疫苗的分子对接分析和载体。使用C-ImmSim服务器模拟和预测候选疫苗的免疫应答。本实验筛选出具有强免疫原性和高保守性的B细胞表位,CTL表位,和具有IFN-γ和IL-4阳性刺突蛋白的Th表位。铁蛋白用作设计候选纳米疫苗的自组装纳米颗粒元件。经过分析,它被发现是可溶的,稳定,非过敏性,并且对其靶受体有很高的亲和力,TLR-3.初步模拟分析结果表明,候选纳米疫苗具有诱导体液和细胞免疫应答的能力。因此,这可能为冠状病毒自组装纳米疫苗的研究提供新的理论基础。它可能是控制和预防PDCoV的有效候选疫苗。
    Based on the whole virus or spike protein of pigs, δ coronavirus (PDCoV) as an immunogen may have unrelated antigenic epitope interference. Therefore, it is essential for screening and identifying advantageous protective antigen epitopes. In addition, immunoinformatic tools are described as an important aid in determining protective antigenic epitopes. In this study, the primary, secondary, and tertiary structures of vaccines were measured using ExPASy, PSIPRED 4.0, and trRosetta servers. Meanwhile, the molecular docking analysis and vector of the candidate nanovaccine were constructed. The immune response of the candidate vaccine was simulated and predicted using the C-ImmSim server. This experiment screened B cell epitopes with strong immunogenicity and high conservation, CTL epitopes, and Th epitopes with IFN-γ and IL-4 positive spike proteins. Ferritin is used as a self-assembled nanoparticle element for designing candidate nanovaccine. After analysis, it has been found to be soluble, stable, non-allergenic, and has a high affinity for its target receptor, TLR-3. The preliminary simulation analysis results show that the candidate nanovaccine has the ability to induce a humoral and cellular immune response. Therefore, it may provide a new theoretical basis for research on coronavirus self-assembled nanovaccines. It may be an effective candidate vaccine for controlling and preventing PDCoV.
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  • 文章类型: Journal Article
    尽管治疗性纳米疫苗在癌症免疫疗法中已经取得了成功,淋巴结归巢能力差等缺点,低抗原呈递效率和低抗肿瘤疗效阻碍了其临床转化。因此,我们通过整合碳点(CD)与肿瘤相关抗原(B16F10和CT26)制备了高级纳米疫苗(CMB和CMC)。这些纳米疫苗可以向前靶向携带LN的肿瘤,诱导激活细胞毒性T细胞(CTL)的强免疫原性,从而容易消除肿瘤细胞并抑制原发/远端肿瘤生长。这项工作提供了一种有希望的治疗性疫苗接种策略来增强癌症免疫疗法。
    Although therapeutic nanovaccines have made a mark in cancer immunotherapy, the shortcomings such as poor homing ability of lymph nodes (LNs), low antigen presentation efficiency and low antitumor efficacy have hindered their clinical transformation. Accordingly, we prepared advanced nanovaccines (CMB and CMC) by integrating carbon dots (CDs) with tumor-associated antigens (B16F10 and CT26). These nanovaccines could forwardly target tumors harbouring LNs, induce strong immunogenicity for activating cytotoxic T cells (CTLs), thereby readily eliminating tumor cells and suppressing primary/distal tumor growth. This work provides a promising therapeutic vaccination strategy to enhance cancer immunotherapy.
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  • 文章类型: Journal Article
    本文献计量学研究对纳米疫苗研究的新兴领域进行了全面分析,利用来自Scopus的数据,并采用首选报告项目进行系统评价和荟萃分析(PRISMA)流程图进行细致的筛选,inclusion,并排除相关研究。利用复杂的文献计量工具,比如Biblioshiny和CiteSpace,我们剖析了大量的文献,以发掘对年度科学产出的批判性见解,确定塑造该领域的关键贡献者和关键出版物。分析描绘了最有影响力的作者,来源,和全球引用的文件,提供该领域的知识结构和增长轨迹的宏观视图。趋势主题和主题映射强调了研究重点的演变,从基本的免疫机制到尖端的纳米材料应用。因子分析和关键词共现网络揭示了文献中复杂的关联和主题集中。该研究的强大方法还确定了表现出最强引文爆发的关键词,标志着学术兴趣浓厚的新兴领域。被引用的作者网络阐明了学者之间的合作模式,而国家合作的时间线网络可视化描绘了纳米疫苗开发中的全球相互作用。至关重要的是,这项研究发现了显著的研究差距和实际意义,提出未来研究的方向,并强调纳米疫苗在公共卫生和个性化医疗中的转化潜力。这种文献计量学调查不仅绘制了当前的景观,而且绘制了纳米疫苗研究轨迹的路线,强调其作为创新免疫治疗策略基石的作用。
    This bibliometric study provides a comprehensive analysis of the burgeoning field of nanovaccine research, leveraging data sourced from Scopus and employing the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flowchart for the meticulous screening, inclusion, and exclusion of relevant studies. Utilizing sophisticated bibliometric tools, such as Biblioshiny and CiteSpace, we dissected the expansive literature to unearth critical insights into the annual scientific output, identifying key contributors and pivotal publications that have shaped the domain. The analysis delineates the most influential authors, sources, and globally cited documents, offering a macroscopic view of the field\'s intellectual structure and growth trajectory. Trend topics and thematic mapping underscored the evolution of research foci, from fundamental immunological mechanisms to cutting-edge nanomaterial applications. Factorial analysis and keyword co-occurrence networks revealed the intricate associations and thematic concentrations within the literature. The study\'s robust methodology also pinpointed the keywords exhibiting the strongest citation bursts, signifying emergent areas of intense academic interest. Networks of cited authors illuminated collaborative patterns among scholars, while timeline network visualizations of country collaborations depicted the global interplay in nanovaccine development. Crucially, this study identified notable research gaps and practical implications, suggesting directions for future investigation and highlighting the translational potential of nanovaccines in public health and personalized medicine. This bibliometric investigation not only maps the current landscape but also charts a course for the trajectory of nanovaccine research, emphasizing its role as a cornerstone of innovative immunotherapeutic strategies.
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  • 文章类型: Journal Article
    衰老的癌细胞具有高免疫原性潜力,已被用于引发抗肿瘤免疫并可能补充抗癌疗法。然而,基于衰老癌细胞的活疫苗接种的功效受到免疫抑制衰老相关分泌表型和衰老细胞促肿瘤能力的干扰的限制.这里,据报道,一种基于衰老癌细胞的纳米疫苗具有强免疫原性和良好的免疫治疗潜力。在增强树突状细胞(DC)内化方面,整合衰老癌细胞膜涂层纳米佐剂的仿生纳米疫苗优于活的衰老癌细胞。改善淋巴结靶向,增强免疫反应。与免疫原性细胞死亡诱导的肿瘤细胞产生的纳米疫苗相反,衰老纳米疫苗促进DC成熟,当与αPD-1组合时,在黑色素瘤攻击的小鼠中引发优异的抗肿瘤保护并改善治疗结果,副作用较少。该研究提出了一种通用的生物制造方法,以最大程度地提高免疫原性潜力并最大程度地减少基于衰老癌细胞的疫苗接种的不利影响,并推进了用于癌症免疫疗法的仿生纳米疫苗的设计。
    Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cancer cell-based vaccination is limited by interference from immunosuppressive senescence-associated secretory phenotype and pro-tumorigenic capacity of senescent cells. Here, a senescent cancer cell-based nanovaccine with strong immunogenicity and favorable potential for immunotherapy is reported. The biomimetic nanovaccine integrating a senescent cancer cell membrane-coated nanoadjuvant outperforms living senescent cancer cells in enhancing dendritic cells (DCs) internalization, improving lymph node targeting, and enhancing immune responses. In contrast to nanovaccines generated from immunogenic cell death-induced tumor cells, senescent nanovaccines facilitate DC maturation, eliciting superior antitumor protection and improving therapeutic outcomes in melanoma-challenged mice with fewer side effects when combined with αPD-1. The study suggests a versatile biomanufacturing approach to maximize immunogenic potential and minimize adverse effects of senescent cancer cell-based vaccination and advances the design of biomimetic nanovaccines for cancer immunotherapy.
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  • 文章类型: Journal Article
    虽然第一代SARS-CoV-2疫苗在COVID-19大流行期间有效地减缓了疾病的传播和严重程度,需要能够诱导针对所关注的新出现的变体的持久和广泛的免疫的疫苗。基于纳米颗粒的疫苗(即,“纳米疫苗”)由聚酸酐纳米颗粒和五嵌段共聚物胶束组成,包括甲型流感病毒,呼吸道合胞病毒,和鼠疫耶尔森氏菌.在这项工作中,设计并优化了含有SARS-CoV-2蛋白和核衣壳抗原的纳米疫苗。优化的纳米疫苗诱导针对野生型SARS-CoV-2病毒的长寿命系统性IgG抗体应答。此外,纳米疫苗诱导的抗体应答能够中和和与多种SARS-CoV-2变体(包括B.1.1.529)交叉反应,以及抗原特异性CD4+和CD8+T细胞应答.最后,纳米疫苗保护小鼠免受致命的SARS-CoV-2攻击,为推进基于颗粒的SARS-CoV-2纳米疫苗奠定了基础。重要声明:第一代SARS-CoV-2疫苗可有效减缓COVID-19的传播并限制其严重程度。然而,目前的疫苗仅靶向病毒的一种抗原(即,刺突蛋白),并专注于中和抗体的产生,这对新的可能不太有效,循环菌株。在这项工作中,我们展示了一种新型纳米疫苗平台的能力,基于聚酐纳米粒子和五嵌段共聚物胶束,对SARS-CoV-2产生持久和广泛的免疫力。这些纳米疫苗诱导持久(>62周)的血清抗体应答,其中和与ACE2受体的结合并且与多种SARS-CoV-2变体交叉反应。此外,用SARS-CoV-2纳米疫苗免疫的小鼠在引流淋巴结和脾脏中显示出抗原特异性T细胞反应的显着增加。一起,这些纳米疫苗诱导的免疫反应有助于保护小鼠免受活的SARS-CoV-2病毒的致命攻击,这表明这种纳米疫苗平台是一种有前途的下一代SARS-CoV-2疫苗。
    While first generation SARS-CoV-2 vaccines were effective in slowing the spread and severity of disease during the COVID-19 pandemic, there is a need for vaccines capable of inducing durable and broad immunity against emerging variants of concern. Nanoparticle-based vaccines (i.e., \"nanovaccines\") composed of polyanhydride nanoparticles and pentablock copolymer micelles have previously been shown to protect against respiratory pathogens, including influenza A virus, respiratory syncytial virus, and Yersinia pestis. In this work, a nanovaccine containing SARS-CoV-2 spike and nucleocapsid antigens was designed and optimized. The optimized nanovaccine induced long-lived systemic IgG antibody responses against wild-type SARS-CoV-2 virus. In addition, the nanovaccine induced antibody responses capable of neutralization and cross-reactivity to multiple SARS-CoV-2 variants (including B.1.1.529) and antigen-specific CD4+ and CD8+ T cell responses. Finally, the nanovaccine protected mice against a lethal SARS-CoV-2 challenge, setting the stage for advancing particle-based SARS-CoV-2 nanovaccines. STATEMENT OF SIGNIFICANCE: First-generation SARS-CoV-2 vaccines were effective in slowing the spread and limiting the severity of COVID-19. However, current vaccines target only one antigen of the virus (i.e., spike protein) and focus on the generation of neutralizing antibodies, which may be less effective against new, circulating strains. In this work, we demonstrated the ability of a novel nanovaccine platform, based on polyanhydride nanoparticles and pentablock copolymer micelles, to generate durable and broad immunity against SARS-CoV-2. These nanovaccines induced long-lasting (> 62 weeks) serum antibody responses which neutralized binding to ACE2 receptors and were cross-reactive to multiple SARS-CoV-2 variants. Additionally, mice immunized with the SARS-CoV-2 nanovaccine showed a significant increase of antigen-specific T cell responses in the draining lymph nodes and spleens. Together, these nanovaccine-induced immune responses contributed to the protection of mice against a lethal challenge of live SARS-CoV-2 virus, indicating that this nanovaccine platform is a promising next-generation SARS-CoV-2 vaccine.
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