Vaccine development

疫苗开发
  • 文章类型: Journal Article
    幽门螺杆菌(H.幽门螺杆菌)是一种传染性细菌,在全球约一半人口的胃中定植。由于其与胃癌发病率增加和胃疾病恶化密切相关,因此被世界卫生组织列为I类致癌物。幽门螺杆菌感染的主要治疗目前包括三联或四联疗法,主要由抗生素和质子泵抑制剂组成。然而,抗生素耐药性的日益普遍对这种方法提出了重大挑战,强调迫切需要有效的疫苗。在这项研究中,利用免疫信息学技术设计了一种新型的多表位幽门螺杆菌疫苗.该疫苗含有来源于9种必需蛋白的表位。软件工具和在线服务器被用来预测,评估,并分析其理化性质,二级和三级结构,和候选疫苗的免疫原性。这些全面的评估最终导致疫苗的最佳设计方案的制定。通过构建基于免疫信息学的新型多表位疫苗,这项研究为预防幽门螺杆菌感染提供了有希望的前景和巨大的潜力.本研究也为开发其他病原体的多表位疫苗提供了参考策略。
    Helicobacter pylori (H. pylori) is an infectious bacterium that colonizes the stomach of approximately half of the global population. It has been classified as a Group I carcinogen by the World Health Organization due to its strong association with an increased incidence of gastric cancer and exacerbation of stomach diseases. The primary treatment for H. pylori infection currently involves triple or quadruple therapy, primarily consisting of antibiotics and proton pump inhibitors. However, the increasing prevalence of antibiotic resistance poses significant challenges to this approach, underscoring the urgent need for an effective vaccine. In this study, a novel multi-epitope H. pylori vaccine was designed using immunoinformatics. The vaccine contains epitopes derived from nine essential proteins. Software tools and online servers were utilized to predict, evaluate, and analyze the physiochemical properties, secondary and tertiary structures, and immunogenicity of the candidate vaccine. These comprehensive assessments ultimately led to the formulation of an optimal design scheme for the vaccine. Through constructing a novel multi-epitope vaccine based on immunoinformatics, this study offers promising prospects and great potential for the prevention of H. pylori infection. This study also provides a reference strategy to develop multi-epitope vaccines for other pathogens.
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  • 文章类型: Journal Article
    卡介苗(BCG)仍然是唯一获得许可的结核病(TB)疫苗。虽然BCG可以预防儿童结核病,它对成人肺结核的保护作用并不理想,开发更好的结核病疫苗是全球卫生优先事项。以前,我们报道了两种重组BCG菌株在免疫功能低下的小鼠和豚鼠中对小鼠结核病有效,毒力和肺部病理。我们最近将这两种重组BCG菌株组合成一种新型候选疫苗(BCGΔBCG1419c::ESAT6-PE25SS),并评估了其免疫原性,小鼠的功效和安全性。这种新的候选疫苗在预防结核病方面不劣于卡介苗,呈现减少的促炎免疫反应,并显示出增强的安全性。
    Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). While BCG protects against TB in children, its protection against pulmonary TB in adults is suboptimal, and the development of a better TB vaccine is a global health priority. Previously, we reported two recombinant BCG strains effective against murine TB with low virulence and lung pathology in immunocompromised mice and guinea pigs. We have recently combined these two recombinant BCG strains into one novel vaccine candidate (BCGΔBCG1419c::ESAT6-PE25SS) and evaluated its immunogenicity, efficacy and safety profile in mice. This new vaccine candidate is non-inferior to BCG in protection against TB, presents reduced pro-inflammatory immune responses and displays an enhanced safety profile.
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  • 文章类型: Journal Article
    基于mRNA技术的疫苗已经取得了巨大的成功,但是它们的特性不一定适合所有病原体。有一种风险是,仅专注于该技术用于新疫苗开发将忽略具有提供更广泛和更持久保护的特性的旧技术。
    Vaccines based on mRNA technology have been tremendously successful, but their properties are not necessarily ideal for all pathogens. There is a risk that concentration on that technology alone for new vaccine development will ignore older technologies that have properties giving broader and more persistent protection.
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  • 文章类型: Journal Article
    百日咳在全球重新出现,在中国发病率上升。控制这种疾病仍然是世界范围内重大的公共卫生挑战。本研究应用文献计量学方法分析了全球和中国对百日咳的研究,评估当前趋势,确定热门话题,预测未来的研究方向,并为科学研究和临床实践提供指导。从四个主要的中文数据库和三个英文数据库中检索了2000年至2023年与百日咳相关的文章。COOC和CiteSpace软件用于分析出版物趋势,地理分布,机构,学科,和关键词,通过网络地图可视化。该研究分析了2,580篇中国文章和5,311篇外国文章和评论。百日咳研究出版物在全球范围内有所增加,国外研究的高峰比中国早。美国在出版量方面领先,而中国在2019年至2023年期间表现出最高的活动爆发。研究主要集中在动物实验,疫苗开发和安全,临床特点和治疗,和百日咳毒素.百日咳研究在全球和中国蓬勃发展。未来的研究应该强调跨分子生物学的跨学科合作,免疫学,和流行病学来创新疫苗和控制策略。此外,治疗药物的持续发展仍然至关重要,因为目前的疫苗不能完全控制百日咳。
    Pertussis has reemerged globally, with rising incidence in China. Controlling this disease remains a significant public health challenge worldwide. This study applies bibliometric methods to analyze global and Chinese research on pertussis, assessing current trends, identifying hot topics, predicting future research directions, and providing guidance for scientific research and clinical practice. Pertussis-related articles from 2000 to 2023 were retrieved from four major Chinese databases and three English databases. COOC and CiteSpace software were used to analyze publication trends, geographic distribution, institutions, disciplines, and keywords, to visualize through network maps. The study analyzed 2,580 Chinese and 5,311 foreign articles and reviews. Pertussis research publications have increased globally, with foreign research peaking earlier than in China. The United States leads in publication volume, while China showed the highest burst of activity from 2019 to 2023. Research mainly focuses on animal experiments, vaccine development and safety, clinical characteristics and treatment, and pertussis toxin. Pertussis research is thriving globally and in China. Future research should emphasize interdisciplinary collaboration across molecular biology, immunology, and epidemiology to innovate vaccines and control strategies. Additionally, continued development of treatment drugs remains crucial as current vaccines do not fully control pertussis.
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  • 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
    背景:登革病毒(DENV)是最广泛的虫媒病毒。世界卫生组织(WHO)宣布登革热为2019年全球十大健康威胁之一。然而,它在文献计量分析中代表性不足。本研究采用文献计量分析来确定研究热点和趋势,全面概述了该领域当前的研究动态。
    结果:我们提供了一份1995年至2023年的报告,该报告提供了登革病毒(DENV)研究的独特纵向分析,揭示了以前文献中未广泛涵盖的重大趋势和变化。共审议了10,767份与DENV相关的文件,随着出版物的显著增加,2021年达到747篇文章的峰值。Plos被忽视的热带病已成为登革热病毒研究的主要杂志,在这一领域发表了791篇文章,是有记录的最高数量。我们的文献计量分析提供了跨多个维度的DENV研究的全面映射,包括媒介生态学,病毒学,和新兴疗法。该研究描绘了一个复杂的免疫反应基因网络,包括IFNA1、DDX58、IFNB1、STAT1、IRF3和NFKB1,突出了重要趋势和新兴主题,特别是气候变化和新爆发对疾病传播的影响。我们的研究结果详细介绍了关键候选疫苗的进展和现状,包括有执照的登瓦夏,更新的疫苗,如Qdenga和TV003,以及更新的临床试验。该研究强调了登革热抗病毒治疗和媒介控制策略的重大进展,强调AT-752和JNJ-1802等创新候选药物,以及用利巴韦林等药物重新利用的潜力,Remdesivir,还有洛匹那韦.此外,它讨论了生物防治方法,包括引入Wolbachia感染的蚊子和基因编辑技术。
    结论:本文献计量研究强调了跨学科合作在推进DENV研究中的关键作用,确定关键趋势和需要进一步探索的领域,包括宿主病毒动力学,抗病毒药物和疫苗的开发和应用,以及人工智能的使用。它主张加强跨学科的伙伴关系,以有效应对DENV带来的挑战。
    BACKGROUND: Dengue virus (DENV) is the most widespread arbovirus. The World Health Organization (WHO) declared dengue one of the top 10 global health threats in 2019. However, it has been underrepresented in bibliometric analyses. This study employs bibliometric analysis to identify research hotspots and trends, offering a comprehensive overview of the current research dynamics in this field.
    RESULTS: We present a report spanning from 1995 to 2023 that provides a unique longitudinal analysis of Dengue virus (DENV) research, revealing significant trends and shifts not extensively covered in previous literature. A total of 10,767 DENV-related documents were considered, with a notable increase in publications, peaking at 747 articles in 2021. Plos Neglected Tropical Diseases has become the leading journal in Dengue virus research, publishing 791 articles in this field-the highest number recorded. Our bibliometric analysis provides a comprehensive mapping of DENV research across multiple dimensions, including vector ecology, virology, and emerging therapies. The study delineates a complex network of immune response genes, including IFNA1, DDX58, IFNB1, STAT1, IRF3, and NFKB1, highlighting significant trends and emerging themes, particularly the impacts of climate change and new outbreaks on disease transmission. Our findings detail the progress and current status of key vaccine candidates, including the licensed Dengvaxia, newer vaccines such as Qdenga and TV003, and updated clinical trials. The study underscores significant advancements in antiviral therapies and vector control strategies for dengue, highlighting innovative drug candidates such as AT-752 and JNJ-1802, and the potential of drug repurposing with agents like Ribavirin, Remdesivir, and Lopinavir. Additionally, it discusses biological control methods, including the introduction of Wolbachia-infected mosquitoes and gene-editing technologies.
    CONCLUSIONS: This bibliometric study underscores the critical role of interdisciplinary collaboration in advancing DENV research, identifying key trends and areas needing further exploration, including host-virus dynamics, the development and application of antiviral drugs and vaccines, and the use of artificial intelligence. It advocates for strengthened partnerships across various disciplines to effectively tackle the challenges posed by DENV.
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  • 文章类型: Journal Article
    细菌中不断增加和持续的抗生素耐药性问题在全球范围内引起了极大的关注,主要是医疗设施。现在,至关重要的是开发一种用于治疗和预防目的的疫苗,以对抗引起医院感染的细菌物种。在许多抗生素耐药的细菌病原体中,阴沟肠杆菌复合体(ECC)包括六个物种,E.科尔卡,E.荒诞,E.Kobie,E.Hormaechei,E.Ludwigi,和E.Nimipressalis,对公众健康有害,并可能使情况恶化。疫苗接种在预防感染和传染病中起着至关重要的作用。这项研究强调了通过检索完整测序的蛋白质组来构建和设计阴沟肠杆菌复合物的多表位疫苗。使用免疫信息学工具评估检索的蛋白质组以选择潜在的疫苗候选物。预测B和T细胞表位以产生体液和细胞免疫,并进一步检查抗原性。变应原性,水溶性,和毒性分析。对最终的潜在表位进行群体覆盖分析。主要组织相容性复合体(MHC)类组合,MHCI类和II类世界人口覆盖率为99.74%,和98.55%分别覆盖了81.81%。一种由佐剂组成的多表位肽疫苗构建体,表位,和接头经受ProtParam工具以计算其物理化学性质。氨基酸总量为236,分子量为27.64kd,疫苗构建体稳定,不稳定性指数为27.01。获得的亲水性(GRAVY)(亲水性)的平均值为-0.659,为更负的并且描绘了亲水性特征。它是非过敏原抗原性的,具有0.8913的抗原性。进一步验证了疫苗构建体与免疫细胞受体MHC-I,MHC-II,和Toll样受体(TLR)-4。分子对接结果描述了所设计的疫苗与对于抗原呈递和加工至关重要的免疫受体具有良好的结合效力。在疫苗-MHC-I中,疫苗-MHC-II,和疫苗-TLR-4复合物,最佳对接姿势分别基于其最低结合能评分-886.8,-995.6和-883.6进行鉴定.总的来说,我们观察到设计的疫苗构建体可以引起适当的免疫反应,并且该构建体可以帮助实验研究人员配制针对目标病原体的疫苗。
    The increasing and ongoing issue of antibiotic resistance in bacteria is of huge concern globally, mainly to healthcare facilities. It is now crucial to develop a vaccine for therapeutic and preventive purposes against the bacterial species causing hospital-based infections. Among the many antibiotic- resistant bacterial pathogens, the Enterobacter cloacae complex (ECC) including six species, E. Colcae, E. absuriae, E. kobie, E. hormaechei, E. ludwigii, and E. nimipressuralis, are dangerous to public health and may worsen the situation. Vaccination plays a vital role in the prevention of infections and infectious diseases. This research highlighted the construction and design of a multi-epitope vaccine for the E. cloacae complex by retrieving their complete sequenced proteome. The retrieved proteome was assessed to opt for potential vaccine candidates using immunoinformatic tools. Both B and T-cell epitopes were predicted in order to create both humoral and cellular immunity and further scrutinized for antigenicity, allergenicity, water solubility, and toxicity analysis. The final potential epitopes were subjected to population coverage analysis. Major histocompatibility complex (MHC) class combined, and MHC Class I and II world population coverage was obtained as 99.74%, and 98.55% respectively while a combined 81.81% was covered. A multi-epitope peptide-based vaccine construct consisting of the adjuvant, epitopes, and linkers was subjected to the ProtParam tool to calculate its physiochemical properties. The total amino acids were 236, the molecular weight was 27.64kd, and the vaccine construct was stable with an instability index of 27.01. The Grand Average of Hydropathy (GRAVY) (hydrophilicity) value obtained was -0.659, being more negative and depicting the hydrophilic character. It was non-allergen antigenic with an antigenicity of 0.8913. The vaccine construct was further validated for binding efficacy with immune cell receptors MHC-I, MHC-II, and Toll-like receptor (TLR)-4. The molecular docking results depict that the designed vaccine has good binding potency with immune receptors crucial for antigen presentation and processing. Among the Vaccine-MHC-I, Vaccine-MHC-II, and Vaccine-TLR-4 complexes, the best-docked poses were identified based on their lowest binding energy scores of -886.8, -995.6, and -883.6, respectively. Overall, we observed that the designed vaccine construct can evoke a proper immune response and the construct could help experimental researchers in the formulation of a vaccine against the targeted pathogens.
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  • 文章类型: Journal Article
    严重发热伴血小板减少综合征(SFTS)是一种新发现的由大别班达病毒(DBV)引起的蜱传病毒性出血热。该病毒于2009年在中国东部首次发现,现在被认为是一种传染病,死亡率从6.3%到30%不等。控制SFTS的最佳策略是开发有效的疫苗。然而,目前没有批准的疫苗可以预防这种疾病,尽管在过去几年中对DBV进行了广泛而深入的研究。本文综述了DBV的结构和诱导的宿主免疫反应,这些是疫苗开发的基本因素。综述了目前DBV疫苗的研究进展。正在开发的DBV疫苗包括蛋白质亚单位疫苗,减毒活疫苗,重组病毒载体疫苗,DNA疫苗。目前,几乎所有的DBV候选疫苗都处于实验室开发或临床前阶段.在成功开发临床批准的DBV疫苗方面仍然存在挑战。
    Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified tick-borne viral hemorrhagic fever caused by Dabie Banda virus (DBV). The virus was first discovered in eastern China in 2009 and is now considered an infectious disease with a mortality rate ranging from 6.3% to 30%. The best strategy for controlling SFTS is to develop effective vaccines. However, no approved vaccines are currently available to prevent this disease, despite the number of extensive and in-depth studies conducted on DBV in the past few years. This review focuses on the structure of DBV and the induced host immune responses which are the fundamental factors in vaccine development, and thoroughly summarizes the current research progress on DBV vaccines. The developing DBV vaccines include protein subunit vaccines, live attenuated vaccines, recombinant virus vector vaccines, and DNA vaccines. At present, almost all candidate vaccines for DBV are in the laboratory development or preclinical stages. There remain challenges in successfully developing clinically approved DBV vaccines.
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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COVID-19大流行,疫苗的重要性已得到广泛认可,并导致研究和开发努力增加。疫苗通过激活免疫系统靶向和破坏癌细胞,在癌症治疗中也起着至关重要的作用。然而,提高癌症疫苗的功效仍然是一个挑战。佐剂,增强对抗原的免疫反应并提高疫苗的有效性,近年来面临着局限性,导致很少的新佐剂被鉴定。人工智能(AI)技术在药物开发中的进步为佐剂筛选和应用提供了基础,导致佐剂的多样化。本文综述了肿瘤疫苗在基础研究和临床治疗中的重要作用,并探讨了使用AI技术从数据库中筛选新型佐剂的方法。这篇综述的发现为下一代疫苗新佐剂的开发提供了有价值的见解。
    With the COVID-19 pandemic, the importance of vaccines has been widely recognized and has led to increased research and development efforts. Vaccines also play a crucial role in cancer treatment by activating the immune system to target and destroy cancer cells. However, enhancing the efficacy of cancer vaccines remains a challenge. Adjuvants, which enhance the immune response to antigens and improve vaccine effectiveness, have faced limitations in recent years, resulting in few novel adjuvants being identified. The advancement of artificial intelligence (AI) technology in drug development has provided a foundation for adjuvant screening and application, leading to a diversification of adjuvants. This article reviews the significant role of tumor vaccines in basic research and clinical treatment and explores the use of AI technology to screen novel adjuvants from databases. The findings of this review offer valuable insights for the development of new adjuvants for next-generation vaccines.
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