Vaccine development

疫苗开发
  • 文章类型: Journal Article
    尽管丙型肝炎病毒(HCV)感染的治疗取得了显著进展,它仍然是一个巨大的全球健康负担,需要开发有效的预防性疫苗。这篇综述论文介绍了HCV疫苗候选和方法的现状,包括更传统的,基于灭活的病毒,更现代,如亚单位蛋白质,矢量化,基于核酸(DNA和mRNA)和病毒样颗粒。HCV疫苗的概念首先放在病毒遗传多样性和对HCV感染的适应性反应的背景下,了解这一点对于指导开发针对这种复杂病毒的有效疫苗至关重要。因为伦理层面在疫苗研究中也很重要,发展,和潜在的部署,我们也在本文中讨论这些问题。由于HCV的遗传变异及其逃避免疫反应的能力,预防HCV感染的安全有效疫苗的道路仍然坎坷。细胞培养系统的进展允许生产灭活的HCV疫苗候选物,可以在体外诱导交叉中和抗体,但是这是否可以预防人类感染尚不清楚。进入临床试验的亚单位蛋白候选疫苗引起HCV特异性体液和细胞反应,尽管它们是否转化为有效预防HCV感染或将感染进展为慢性状态仍有待证明。这种反应也是由经过临床试验的基于载体的候选疫苗诱导的。降低了病毒HCV载量,但不能预防慢性HCV感染。从临床前动物研究中不容易预测这些失望。使用病毒样颗粒的疫苗平台,DNA,mRNA为HCV疫苗提供了机会,但是他们在这方面的潜力还没有显示出来。确保设计的疫苗基于保守表位并引发广泛的中和免疫应答也是必需的。鉴于开发预防性HCV疫苗的失败,继续支持国家战略至关重要,包括筛查和治疗计划的资金。然而,这些行动可能不足以永久控制HCV负担,鼓励进一步动员大量资源用于HCV疫苗研究,作为消除病毒性肝炎作为全球公共卫生的缺失因素。
    Despite remarkable progress in the treatment of hepatitis C virus (HCV) infection, it remains a significant global health burden, necessitating the development of an effective prophylactic vaccine. This review paper presents the current landscape of HCV vaccine candidates and approaches, including more traditional, based on inactivated virus, and more modern, such as subunit protein, vectored, based on nucleic acids (DNA and mRNA) and virus-like particles. The concept of the HCV vaccine is first put in the context of viral genetic diversity and adaptive responses to HCV infection, an understanding of which is crucial in guiding the development of an effective vaccine against such a complex virus. Because ethical dimensions are also significant in vaccine research, development, and potential deployment, we also address them in this paper. The road to a safe and effective vaccine to prevent HCV infection remains bumpy due to the genetic variation of HCV and its ability to evade immune responses. The progress in cell-culture systems allowed for the production of an inactivated HCV vaccine candidate, which can induce cross-neutralizing antibodies in vitro, but whether this could prevent infection in humans is unknown. Subunit protein vaccine candidates that entered clinical trials elicited HCV-specific humoral and cellular responses, though it remains to be shown whether they translate into effective prevention of HCV infection or progression of infection to a chronic state. Such responses were also induced by a clinically tested vector-based vaccine candidate, which decreased the viral HCV load but did not prevent chronic HCV infection. These disappointments were not readily predicted from preclinical animal studies. The vaccine platforms employing virus-like particles, DNA, and mRNA provide opportunities for the HCV vaccine, but their potential in this context has yet to be shown. Ensuring the designed vaccine is based on conserved epitope(s) and elicits broadly neutralizing immune responses is also essential. Given failures in developing a prophylactic HCV vaccine, it is crucial to continue supporting national strategies, including funding for screening and treatment programs. However, these actions are likely insufficient to permanently control the HCV burden, encouraging further mobilization of significant resources for HCV vaccine research as a missing element in the elimination of viral hepatitis as a global public health.
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  • 文章类型: Journal Article
    单纯疱疹病毒(HSV),一种威胁全球公共卫生的流行人类病原体,因其复杂的发病机制而声名狼藉,包括粘膜细胞的溶解性感染,神经元内的潜伏感染,和定期重新激活。这种复杂的相互作用,再加上HSV复杂的免疫逃避策略,引起各种疾病,包括生殖器病变,新生儿脑炎,和癌症。尽管进行了70多年的不懈研究,针对HSV的有效预防或治疗疫苗尚未出现,主要是由于对病毒与宿主相互作用的了解有限,这反过来又阻碍了有效疫苗靶标的识别。然而,HSV独特的病理特征,包括其巨大的遗传负荷能力,高可复制性,可传播性,和神经嗜性,使其成为各种应用的有希望的候选者,跨越溶瘤病毒疗法,基因和免疫疗法,甚至作为神经科学的成像示踪剂。在这次审查中,我们全面更新了HSV发病机制和免疫逃避的最新突破,批判性总结候选疫苗开发的进展,并讨论了HSV作为生物工具的多方面应用。重要的是,我们强调成功和挑战,强调迫切需要加强对HSV的研究,目的是提供更深入的见解,不仅可以推进HSV治疗策略,还可以拓宽其应用范围。
    Herpes simplex virus (HSV), an epidemic human pathogen threatening global public health, gains notoriety for its complex pathogenesis that encompasses lytic infection of mucosal cells, latent infection within neurons, and periodic reactivation. This intricate interplay, coupled with HSV\'s sophisticated immune evasion strategies, gives rise to various diseases, including genital lesions, neonatal encephalitis, and cancer. Despite more than 70 years of relentless research, an effective preventive or therapeutic vaccine against HSV has yet to emerge, primarily due to the limited understanding of virus-host interactions, which in turn impedes the identification of effective vaccine targets. However, HSV\'s unique pathological features, including its substantial genetic load capacity, high replicability, transmissibility, and neurotropism, render it a promising candidate for various applications, spanning oncolytic virotherapy, gene and immune therapies, and even as an imaging tracer in neuroscience. In this review, we comprehensively update recent breakthroughs in HSV pathogenesis and immune evasion, critically summarize the progress made in vaccine candidate development, and discuss the multifaceted applications of HSV as a biological tool. Importantly, we highlight both success and challenges, emphasizing the critical need for intensified research into HSV, with the aim of providing deeper insights that can not only advance HSV treatment strategies but also broaden its application horizons.
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  • 文章类型: Journal Article
    随着纳米技术的出现,疫苗的发展进入了一个新时代,特别是通过利用纳米粒子。本文综述了纳米颗粒在增强mRNA疫苗疗效和稳定性方面的作用。纳米颗粒,由于其独特的特性,如高表面积,可调大小,以及它们被功能化的能力,已经成为疫苗开发的有力工具。具体来说,脂质纳米颗粒(LNPs)通过保护脆弱的mRNA分子并促进其被细胞有效吸收,彻底改变了mRNA疫苗的递送。这篇综述讨论了mRNA疫苗制剂中使用的各种类型的纳米颗粒,包括基于脂质的,聚合物基,和无机纳米粒子,强调他们的优势和局限性。此外,它探索了纳米粒子改善免疫反应的机制,例如增强的抗原呈递和mRNA的延长释放。这篇综述还讨论了纳米颗粒疫苗开发的挑战和未来方向。强调需要进一步研究以优化配方以实现更广泛的应用。通过深入分析纳米颗粒在mRNA疫苗中的当前进展和潜力,这篇综述旨在阐明它们在抗击传染病和改善公共卫生结果方面的关键作用。
    The development of vaccines has entered a new era with the advent of nanotechnology, particularly through the utilization of nanoparticles. This review focuses on the role of nanoparticles in enhancing the efficacy and stability of mRNA vaccines. Nanoparticles, owing to their unique properties such as high surface area, tunable size, and their ability to be functionalized, have emerged as powerful tools in vaccine development. Specifically, lipid nanoparticles (LNPs) have revolutionized the delivery of mRNA vaccines by protecting the fragile mRNA molecules and facilitating their efficient uptake by cells. This review discusses the various types of nanoparticles employed in mRNA vaccine formulations, including lipid-based, polymer-based, and inorganic nanoparticles, highlighting their advantages and limitations. Moreover, it explores the mechanisms by which nanoparticles improve immune responses, such as enhanced antigen presentation and the prolonged release of mRNA. This review also addresses the challenges and future directions in nanoparticle-based vaccine development, emphasizing the need for further research to optimize formulations for broader applications. By providing an in-depth analysis of the current advancements in and potential of nanoparticles in mRNA vaccines, this review aims to shed light on their critical role in combating infectious diseases and improving public health outcomes.
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  • 文章类型: Journal Article
    尼帕病毒(NiV)是一种新兴的病原体,可引起脑炎,并在受感染的受试者中引起高死亡率。本系统综述旨在全面分析NiV的全球流行病学和研究进展,以确定文献中的关键知识空白。使用文献数据库搜索的文章,即PubMed,Scopus,WebofScience,和科学直接发表了5596篇文章。文章筛选后,本系统综述共包括97篇文章,包括41项流行病学研究和56项关于NiV的研究进展。大多数NiV流行病学研究是在孟加拉国进行的,反映了该国NiV爆发的沉重负担。1998年在马来西亚发现了最初的NiV爆发,随后在孟加拉国报告了爆发,印度,和菲律宾。传输路线因国家而异,主要通过马来西亚的猪,孟加拉国的椰枣汁消费,和人对人在印度。然而,NiV基因组序列的可用性仍然有限,特别是来自马来西亚和印度。死亡率也因国家而异,孟加拉国超过70%,印度,菲律宾,马来西亚不到40%。了解各国死亡率的差异对于通报NiV流行病学和加强疫情预防和管理策略至关重要。在研究发展方面,大多数研究集中在疫苗开发上,其次是系统发育分析和抗病毒研究。虽然许多疫苗和抗病毒药物在动物模型中表现出完全的保护作用,只有两种疫苗进入临床试验。系统发育分析揭示了马来西亚NiV之间的不同进化枝,NiV孟加拉国,和NiV印度,提议将NiV印度归类为与NiV孟加拉国分开的菌株。一起来看,整合疾病监测和研究的全面OneHealth方法对于未来的NiV研究至关重要。扩展NiV基因组序列的数据集,特别是来自马来西亚,孟加拉国,印度将是关键。这些研究工作对于提高我们对NiV致病性的理解和开发强大的诊断分析至关重要。有效准备和应对未来NiV爆发所需的疫苗和治疗。
    Nipah virus (NiV) is an emerging pathogen that causes encephalitis and a high mortality rate in infected subjects. This systematic review aimed to comprehensively analyze the global epidemiology and research advancements of NiV to identify the key knowledge gaps in the literature. Articles searched using literature databases, namely PubMed, Scopus, Web of Science, and Science Direct yielded 5,596 articles. After article screening, 97 articles were included in this systematic review, comprising 41 epidemiological studies and 56 research developments on NiV. The majority of the NiV epidemiological studies were conducted in Bangladesh, reflecting the country\'s significant burden of NiV outbreaks. The initial NiV outbreak was identified in Malaysia in 1998, with subsequent outbreaks reported in Bangladesh, India, and the Philippines. Transmission routes vary by country, primarily through pigs in Malaysia, consumption of date palm juice in Bangladesh, and human-to-human in India. However, the availability of NiV genome sequences remains limited, particularly from Malaysia and India. Mortality rates also vary according to the country, exceeding 70% in Bangladesh, India, and the Philippines, and less than 40% in Malaysia. Understanding these differences in mortality rate among countries is crucial for informing NiV epidemiology and enhancing outbreak prevention and management strategies. In terms of research developments, the majority of studies focused on vaccine development, followed by phylogenetic analysis and antiviral research. While many vaccines and antivirals have demonstrated complete protection in animal models, only two vaccines have progressed to clinical trials. Phylogenetic analyses have revealed distinct clades between NiV Malaysia, NiV Bangladesh, and NiV India, with proposals to classify NiV India as a separate strain from NiV Bangladesh. Taken together, comprehensive OneHealth approaches integrating disease surveillance and research are imperative for future NiV studies. Expanding the dataset of NiV genome sequences, particularly from Malaysia, Bangladesh, and India will be pivotal. These research efforts are essential for advancing our understanding of NiV pathogenicity and for developing robust diagnostic assays, vaccines and therapeutics necessary for effective preparedness and response to future NiV outbreaks.
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  • 文章类型: Journal Article
    牙周炎是一种常见的多微生物疾病。它损伤软组织和牙槽骨,并造成重大的公共卫生负担。开发先进的治疗方法和探索针对牙周炎的疫苗有望成为潜在的治疗途径。缺乏牙周炎疫苗的临床试验。因此,至关重要的是,迫切需要制定战略,在公共卫生的初级预防层面实施疫苗。对疫苗作用原理和机制的深刻理解对疫苗的成功开发及其临床转化起着至关重要的作用。这篇综述旨在为开发高效牙周炎疫苗提供一个全面的总结。此外,我们解决了这些努力的局限性,并探索了开发有效的牙周炎疫苗的未来可能性。
    Periodontitis is a prevalent polymicrobial disease. It damages soft tissues and alveolar bone, and causes a significant public-health burden. Development of an advanced therapeutic approach and exploration of vaccines against periodontitis hold promise as potential treatment avenues. Clinical trials for a periodontitis vaccine are lacking. Therefore, it is crucial to address the urgent need for developing strategies to implement vaccines at the primary level of prevention in public health. A deep understanding of the principles and mechanisms of action of vaccines plays a crucial role in the successful development of vaccines and their clinical translation. This review aims to provide a comprehensive summary of potential directions for the development of highly efficacious periodontitis vaccines. In addition, we address the limitations of these endeavors and explore future possibilities for the development of an efficacious vaccine against periodontitis.
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  • 文章类型: Journal Article
    腺病毒是无包膜DNA病毒,可引起多种症状,从轻度感染到各种宿主中威胁生命的疾病。由于这些病毒的独特特性,它们也已成为基因转移和癌症治疗工具的载体。腺病毒载体可通过修饰野生型病毒使其具有复制缺陷而用于基因治疗。这使得可以将特定的病毒基因换成携带治疗基因的区段,并将所得载体用作将基因递送至特定组织的手段。在这次审查中,我们概述了腺病毒载体的逐步发展,探索他们的特点,遗传修饰,以及在临床和临床前环境中的使用范围。一个重要的重点是他们在推进基因治疗中的关键作用,癌症治疗,免疫疗法,以及各种疾病疫苗开发的最新突破。
    Adenoviruses are non-enveloped DNA viruses that cause a wide range of symptoms, from mild infections to life-threatening diseases in a broad range of hosts. Due to the unique characteristics of these viruses, they have also become a vehicle for gene-transfer and cancer therapeutic instruments. Adenovirus vectors can be used in gene therapy by modifying wild-type viruses to render them replication-defective. This makes it possible to swap out particular viral genes for segments that carry therapeutic genes and to employ the resultant vector as a means of delivering genes to specified tissues. In this review, we outline the progressive development of adenovirus vectors, exploring their characteristics, genetic modifications, and range of uses in clinical and preclinical settings. A significant emphasis is placed on their crucial role in advancing gene therapy, cancer therapy, immunotherapy, and the latest breakthroughs in vaccine development for various diseases.
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  • 文章类型: Journal Article
    肺炎克雷伯菌,一种突出的医院病原体,由于其多重耐药(MDR)和高毒力菌株,构成了严重的全球健康威胁。这篇全面的综述集中在针对肺炎克雷伯菌疫苗开发中采取的复杂方法。传统方法,如全细胞和核糖体疫苗,与现代战略相比,包括DNA和mRNA疫苗,和细胞外囊泡(EV),在其他人中。每种方法都有独特的优势和挑战,强调开发针对这种病原体的有效疫苗的复杂性。计算工具和人工智能(AI)的重大进步彻底改变了抗原识别和疫苗设计,提高开发多表位疫苗的精度和效率。该综述还强调了糖组学和免疫信息学在鉴定关键抗原成分和阐明肺炎克雷伯菌所采用的免疫逃避机制方面的潜力。尽管取得了进展,在确保安全方面仍然存在挑战,功效,以及这些疫苗的可制造性。值得注意的是,电动汽车由于其固有的佐剂特性和引发强大免疫反应的能力而显示出希望。尽管对炎症和抗原变异性的担忧仍然存在。这篇综述提供了肺炎克雷伯菌疫苗开发现状的重要概述。强调需要持续创新和跨学科合作,以解决这一紧迫的公共卫生问题。先进的计算方法和人工智能的整合具有加速开发有效免疫疗法的潜力。为新型抗多药肺炎克雷伯菌疫苗铺平了道路。
    Klebsiella pneumoniae, a prominent nosocomial pathogen, poses a critical global health threat due to its multidrug-resistant (MDR) and hypervirulent strains. This comprehensive review focuses into the complex approaches undertaken in the development of vaccines against K. pneumoniae. Traditional methods, such as whole-cell and ribosomal-based vaccines, are compared with modern strategies, including DNA and mRNA vaccines, and extracellular vesicles (EVs), among others. Each method presents unique advantages and challenges, emphasising the complexity of developing an effective vaccine against this pathogen. Significant advancements in computational tools and artificial intelligence (AI) have revolutionised antigen identification and vaccine design, enhancing the precision and efficiency of developing multiepitope-based vaccines. The review also highlights the potential of glycomics and immunoinformatics in identifying key antigenic components and elucidating immune evasion mechanisms employed by K. pneumoniae. Despite progress, challenges remain in ensuring the safety, efficacy, and manufacturability of these vaccines. Notably, EVs demonstrate promise due to their intrinsic adjuvant properties and ability to elicit robust immune responses, although concerns regarding inflammation and antigen variability persist. This review provides a critical overview of the current landscape of K. pneumoniae vaccine development, stressing the need for continued innovation and interdisciplinary collaboration to address this pressing public health issue. The integration of advanced computational methods and AI holds the potential to accelerate the development of effective immunotherapies, paving the way for novel vaccines against MDR K. pneumoniae.
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  • 文章类型: Journal Article
    疫苗开发是公共卫生工作的基石,在遏制传染病和降低全球发病率和死亡率方面至关重要。然而,传统的疫苗开发方法通常很耗时,昂贵的,效率低下。人工智能(AI)的出现开启了疫苗设计的新纪元,提供前所未有的机会来加快这一进程。这篇叙述性综述探讨了人工智能在疫苗开发中的作用,专注于抗原选择,表位预测,佐剂鉴定,和优化策略。AI算法,包括机器学习和深度学习,利用基因组数据,蛋白质结构,和免疫系统相互作用来预测抗原表位,评估免疫原性,并优先考虑抗原进行实验。此外,AI驱动的方法促进了免疫原的合理设计和具有最佳安全性和功效谱的新型佐剂候选物的鉴定。数据异质性等挑战,模型可解释性,必须解决监管方面的问题,以实现人工智能在疫苗开发中的全部潜力。整合新兴技术,如单细胞组学和合成生物学,承诺提高疫苗设计的准确性和可扩展性。这篇综述强调了人工智能对疫苗开发的变革性影响,并强调了跨学科合作和监管协调的必要性,以加快针对传染病的安全有效疫苗的交付。
    Vaccine development stands as a cornerstone of public health efforts, pivotal in curbing infectious diseases and reducing global morbidity and mortality. However, traditional vaccine development methods are often time-consuming, costly, and inefficient. The advent of artificial intelligence (AI) has ushered in a new era in vaccine design, offering unprecedented opportunities to expedite the process. This narrative review explores the role of AI in vaccine development, focusing on antigen selection, epitope prediction, adjuvant identification, and optimization strategies. AI algorithms, including machine learning and deep learning, leverage genomic data, protein structures, and immune system interactions to predict antigenic epitopes, assess immunogenicity, and prioritize antigens for experimentation. Furthermore, AI-driven approaches facilitate the rational design of immunogens and the identification of novel adjuvant candidates with optimal safety and efficacy profiles. Challenges such as data heterogeneity, model interpretability, and regulatory considerations must be addressed to realize the full potential of AI in vaccine development. Integrating emerging technologies, such as single-cell omics and synthetic biology, promises to enhance vaccine design precision and scalability. This review underscores the transformative impact of AI on vaccine development and highlights the need for interdisciplinary collaborations and regulatory harmonization to accelerate the delivery of safe and effective vaccines against infectious diseases.
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  • 文章类型: Journal Article
    癌症的特点是无限的增殖和转移,传统的治疗策略通常会导致耐药性的产生,从而凸显了对更个性化治疗的需求。mRNA疫苗通过转录和翻译将外源靶抗原的基因序列转移到人细胞中,以刺激机体产生针对编码蛋白的特异性免疫反应,从而使机体获得针对所述抗原的免疫保护;这种方法可用于个性化癌症治疗。自从最近的冠状病毒大流行以来,mRNA疫苗的开发已经取得了实质性进展和广泛采用。在本次审查中,mRNA疫苗的发展,他们的行动机制,对影响其功能的因素和目前疫苗的临床应用进行了讨论。重点放在mRNA疫苗在癌症中的应用上,旨在强调这种新颖且有前途的治疗方法的独特进展和剩余挑战。
    Cancer is characterized by unlimited proliferation and metastasis, and traditional therapeutic strategies usually result in the acquisition of drug resistance, thus highlighting the need for more personalized treatment. mRNA vaccines transfer the gene sequences of exogenous target antigens into human cells through transcription and translation to stimulate the body to produce specific immune responses against the encoded proteins, so as to enable the body to obtain immune protection against said antigens; this approach may be adopted for personalized cancer therapy. Since the recent coronavirus pandemic, the development of mRNA vaccines has seen substantial progress and widespread adoption. In the present review, the development of mRNA vaccines, their mechanisms of action, factors influencing their function and the current clinical applications of the vaccine are discussed. A focus is placed on the application of mRNA vaccines in cancer, with the aim of highlighting unique advances and the remaining challenges of this novel and promising therapeutic approach.
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  • 文章类型: Journal Article
    2019年,估计有495万人死亡与抗菌素耐药性(AMR)有关。疫苗可以通过避免药物敏感性和耐药性感染来预防许多此类死亡。减少抗生素的使用,并降低产生抗性基因的可能性。然而,它们在减轻AMR方面的作用目前未得到充分利用。本文基于先前的研究,利用疫苗价值概况-评估健康状况的工具,社会经济,以及病原体的社会影响-为疫苗开发提供信息。我们分析了16种病原体的影响,疫苗价值概况涵盖,在AMR上,并探索疫苗如何降低AMR。本文还提供了有关疫苗开发和使用的见解。疫苗对于减轻传染病的影响和遏制AMR的发展至关重要。为了充分发挥他们的潜力,疫苗必须在对抗AMR的总体战略中更加突出。这需要持续投资于新疫苗的研究和开发,并实施更多的预防和控制措施,以有效应对这一全球威胁。
    In 2019, an estimated 4.95 million deaths were linked to antimicrobial resistance (AMR). Vaccines can prevent many of these deaths by averting both drug-sensitive and resistant infections, reducing antibiotic usage, and lowering the likelihood of developing resistance genes. However, their role in mitigating AMR is currently underutilized. This article builds upon previous research that utilizes Vaccine Value Profiles-tools that assess the health, socioeconomic, and societal impact of pathogens-to inform vaccine development. We analyze the effects of 16 pathogens, covered by Vaccine Value Profiles, on AMR, and explore how vaccines could reduce AMR. The article also provides insights into vaccine development and usage. Vaccines are crucial in lessening the impact of infectious diseases and curbing the development of AMR. To fully realize their potential, vaccines must be more prominently featured in the overall strategy to combat AMR. This requires ongoing investment in research and development of new vaccines and the implementation of additional prevention and control measures to address this global threat effectively.
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