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Intranasal Delivery of Liposomes-Based Lipopeptide Hookworm Vaccine Diminished its Ability to Protect Mice Against Hookworm Challenge 以脂质体为基础的脂肽钩虫疫苗鼻内递送降低了其保护小鼠免受钩虫攻击的能力
Pub Date : 2022-12-30 DOI: 10.17140/vroj-6-118
Stacey Bartlett, R. Eichenberger, Ahmed O Shalash, A. Loukas, M. Skwarczynski, I. Toth, W. M. Hussein
Background Hookworm infection is particularly problematic for middle- to low-income countries. While treatment methods are currently available, vaccination may be the ideal intervention, as it could offer cost-effective long-term protection against infection and reinfection. Methods Previously established lipopeptide-based vaccine formulations, proven to be effective in an oral application, were adapted for an intranasal administration using a predicted B-cell peptide epitope derived from the hookworm Necator americanus aspartic protease-1 (Na-APR-1) protein and a universal T-helper epitope attached to two lipid moieties, Pam2Cys or lipid core peptide (LCP). The lipopeptides were encapsulated into liposomes or self-assembled into nanoparticles. The intranasal vaccine candidates were evaluated in a rodent hookworm challenge model. Results The vaccine candidates were formulated to optimal sizes and charges for uptake by immune cells. However, no significant serum antibody response was elicited, and no protection was demonstrated following hookworm challenge. Conclusion In contrast to the previously reported effective oral immunization, intranasal delivery of lipopeptide-based vaccine failed to trigger significant antibody responses in mice against hookworm and had no effect on parasite numbers following challenge infection.
钩虫感染在中低收入国家尤其成问题。虽然目前有治疗方法,但疫苗接种可能是理想的干预措施,因为它可以提供具有成本效益的长期保护,防止感染和再感染。方法先前建立的以脂肽为基础的疫苗制剂,经证明口服有效,适用于鼻内给药,使用来自钩虫美洲Necator aspartic蛋白酶-1 (Na-APR-1)蛋白的预测b细胞肽表位和附着于两个脂质片段Pam2Cys或脂质核心肽(LCP)的通用t辅助表位。脂肽被包被脂质体或自组装成纳米颗粒。在啮齿动物钩虫攻毒模型中对鼻内候选疫苗进行了评估。结果制备出适合免疫细胞吸收的候选疫苗。然而,没有引起明显的血清抗体反应,也没有显示出钩虫攻击后的保护作用。结论与先前报道的有效口服免疫相比,鼻内注射基于脂肽的疫苗未能在小鼠体内引发针对钩虫的显著抗体反应,并且对攻毒感染后的寄生虫数量没有影响。
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引用次数: 0
The Future Direction of Cancer Vaccines: An Editorial 癌症疫苗的未来方向:一篇社论
Pub Date : 2022-12-30 DOI: 10.17140/vroj-6-e007
N. Khansari
In the past, vaccines were defined as prophylactic entities. Today, there are two types of vaccines: prophylactic for prevention, and therapeutic for the treatment of infections or cancers. Therapeutic cancer vaccine, in fact, represents an option for active immunotherapy for the treatment of late-stage and/or prevention of recurrent diseases.1
过去,疫苗被定义为预防实体。今天,有两种类型的疫苗:用于预防的预防性疫苗和用于治疗感染或癌症的治疗性疫苗。事实上,治疗性癌症疫苗代表了主动免疫治疗的一种选择,用于治疗晚期和/或预防复发性疾病
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引用次数: 0
Model Liposomal Delivery System for Drugs and Vaccines 药物和疫苗的模型脂质体递送系统
Pub Date : 2020-12-31 DOI: 10.17140/vroj-5-117
F. Firdaus, Zeinab G. Khalil, R. Capon, M. Skwarczynski, I. Toth
Background Liposomes have been used for drug delivery since their discovery 60-years-ago. The advantages they provide as carriers have been recognised and exploited to improve the delivery of numerous drugs and eliminate harmful side-effects. Liposomal delivery has been tested for anticancer drugs, anti-tuberculosis drugs, variety of vaccines, just to list a few. Methods We developed a series of liposomal formulations with the addition of cholesterol and polyethylene glycol. The uptake of these formulations by human epithelial prostate cancer (PC-3) cells and mouse macrophages was examined and analysed by flow cytometry and confocal microscopy. Results Among the liposomes tested, small anionic liposome vesicles (≤200 nm) prepared with egg phosphatidylglycerol as the main lipid were most effectively taken up by PC-3 cells and macrophages. Conclusion We produced a liposome formulation that can be used as a model system for the delivery of drugs and vaccines.
自从60年前脂质体被发现以来,就一直被用于药物输送。它们作为载体提供的优势已经被认识到,并被用于改善许多药物的输送和消除有害的副作用。脂质体输送已被用于抗癌药物、抗结核药物、各种疫苗的测试,仅举几例。方法研制了一系列添加胆固醇和聚乙二醇的脂质体制剂。用流式细胞术和共聚焦显微镜检测和分析了人前列腺癌上皮细胞(PC-3)和小鼠巨噬细胞对这些制剂的摄取情况。结果以卵磷脂酰甘油为主要脂质制备的阴离子小脂质体囊泡(≤200 nm)最容易被PC-3细胞和巨噬细胞吸收。结论制备的脂质体制剂可作为药物和疫苗递送的模型系统。
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引用次数: 1
Recombinant Protein D from Haemophilus influenzae Induces Mouse Bactericidal Antibodies Against Typeable and Non-Typeable Haemophilus influenzae, which Partially Protect Infant Rats Against Serotype b Bacteraemia 流感嗜血杆菌重组蛋白D诱导小鼠抗可分型和不可分型流感嗜血杆菌的杀菌抗体,部分保护幼鼠抗血清型b型菌血症
Pub Date : 2020-12-31 DOI: 10.17140/vroj-5-116
N. Palmer, Yajun Tan, Manolya Saydam, Arif Felek, Huajie Zhang, Shumin Zhang, Min Fang, J. Wheeler, Qiming Hou, Xiao Ma, Junzhi Wang, F. Mawas
Aim To evaluate the immunogenicity of a recombinant protein D from Haemophilus Influenzae (Hi) and the functional activities of the induced protein D antibodies in a mouse model. Methods Female Balb/c mice were immunised subcutaneously with recombinant protein D in the presence or absence of adjuvants and the serum immunoglobulin G (IgG) response to protein D was assessed by ELISA. The functional activity of the immune sera was evaluated in vitro using bactericidal assay against typeable Hi serotype b (Hib) and non-typeable Hi (NTHi) clinical isolates and in vivo using an infant rat bacteraemia model and a Hib clinical isolate. Results A dose-dependent IgG response was induced in mice immunised with the recombinant protein D and this response was further increased by the adjuvants used [CPG, AlPO4 and Al(OH)3], with the latter showing the greatest effect on the antibody response. Immune sera were very effective in bactericidal assay against several Hib and NTHi clinical isolates, with a higher serum bactericidal titre against the NTHi than against the Hib isolates. This is possibly due to the lower expression of protein D on the Hib isolates used in our study, compared to the NTHi isolates. In addition, anti-protein D antibodies were partially protective in vivo infant rat bacteraemia model against a challenge with Hib Eagan strain. Conclusion Our results suggest that recombinant protein D is a good vaccine candidate against Hi and should be given in combination with other vaccine candidates to ensure complete protection against Hib and NTHi.
目的评价流感嗜血杆菌重组蛋白D在小鼠模型中的免疫原性及其诱导的蛋白D抗体的功能活性。方法在有或无佐剂的情况下,用重组蛋白D皮下免疫雌性Balb/c小鼠,ELISA法检测血清免疫球蛋白G (IgG)对蛋白D的反应。免疫血清的功能活性在体外通过对可分型乙型肝炎(Hib)和不可分型乙型肝炎(NTHi)临床分离株的杀菌试验进行评估,在体内使用婴儿大鼠菌血症模型和Hib临床分离株进行评估。结果重组蛋白D免疫小鼠产生剂量依赖性IgG应答,并通过佐剂[CPG、AlPO4和Al(OH)3]进一步增强IgG应答,其中Al(OH)3对抗体应答的影响最大。免疫血清对几种Hib和NTHi临床分离株的杀菌试验非常有效,对NTHi的血清杀菌滴度高于对Hib分离株的血清杀菌滴度。这可能是由于与NTHi分离株相比,我们研究中使用的Hib分离株上蛋白D的表达较低。此外,抗蛋白D抗体在体内大鼠菌血症模型中对Hib Eagan菌株的攻击具有部分保护作用。结论重组蛋白D是一种很好的抗Hi候选疫苗,可与其他候选疫苗联合使用,以确保对Hib和NTHi具有完全的保护作用。
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引用次数: 0
Analysis of Antibiotic Resistance of the Probiotic Bacteria Found in Commercial Food Products 商品食品中益生菌的抗生素耐药性分析
Pub Date : 2019-12-31 DOI: 10.17140/vroj-4-115
R. Priyadarshana, Clarencia R. Daniel
Aim The Lactobacillus is an industrially-important group of probiotic organisms that plays an important role in human health by inhibiting harmful and pathogenic bacterial growth, boosting immune function, and increasing resistance to infection. The aim of this study was to identify the probiotic bacteria Lactobacillus based on their phenotypic features and genotypic features. This study also shows the importance of probiotic bacterium, and the effects of their antibiotic resistance to human. Method Six different brands were cultured on man, rogosa and sharpe (MRS) agar. The identity of the culture was based on the characteristics of the strains of Lactobacillus spp. which was characterized using their phenotypic features (cell morphology, Gram’s staining tests which are specific for Lactobacillus genus). The bacterial deoxyribonucleic acid (DNA) was extracted by two different methods, boiled cell method and cetyl trimethylammonium bromide (CTAB) method. Furthermore, the extracted DNA yields were compared to determine which gives the best yield. The bacterial genus was detected with using genus specific primers, specific to the Lactobacillus. All the isolates were further subjected to antibiotic resistance test using disc diffusion method against a total of 4 antibiotics (Erythromycin, Tetracycline, Vancomycin and Ampicillin) and the antibiotic resistant genes of tet(M) & erm(B), were analyzed by polymerase chain reaction (PCR). Results Five isolates out of six samples (A to E) were found to exhibit multiple resistance against some of the most commonly used antibiotics. The isolates showed resistance toward tetracycline, erythromycin & vancomycin. Besides that, the isolates displayed a low-level of resistance toward ampicillin. Conclusion This study proves that antibiotic resistance is present in different species of probiotic strains, which may pose a food safety concern.
乳酸杆菌是一种重要的工业益生菌,通过抑制有害细菌和致病菌的生长,增强免疫功能,增强对感染的抵抗力,对人体健康起着重要作用。本研究的目的是根据益生菌乳酸菌的表型特征和基因型特征对其进行鉴定。这项研究也显示了益生菌的重要性,以及它们对人类抗生素耐药性的影响。方法在man、rogosa和sharpe (MRS)琼脂上培养6种不同的菌种。培养物的鉴定是基于乳酸菌属菌株的特征,利用它们的表型特征(细胞形态,革兰氏染色试验,这是乳酸菌属特有的)来表征。采用水煮细胞法和十六烷基三甲基溴化铵法提取细菌脱氧核糖核酸(DNA)。此外,提取的DNA产量进行比较,以确定哪一个给出最好的产量。采用乳杆菌属特异性引物对细菌属进行检测。采用圆盘扩散法对4种抗生素(红霉素、四环素、万古霉素和氨苄西林)进行耐药试验,并采用聚合酶链反应(PCR)分析tet(M)和erm(B)的耐药基因。结果6份样本中有5株(A ~ E)对一些常用抗生素出现多重耐药。分离株对四环素、红霉素和万古霉素均有耐药性。此外,分离株对氨苄西林表现出低水平的耐药。结论不同种类的益生菌均存在抗生素耐药性,可能引起食品安全问题。
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引用次数: 1
A Review of Vaccine Efficacy Measures 疫苗有效性指标综述
Pub Date : 2019-12-31 DOI: 10.17140/vroj-4-110
Sayan Dasgupta
To fully understand the assessments of vaccine efficacy and safety, the crucial information needed for regulatory approval, one must understand the principles of vaccine epidemiology. In this review article, we go through some of the key concepts in vaccine epidemiology
要充分了解疫苗效力和安全性评估,这是监管部门批准所需的关键信息,就必须了解疫苗流行病学原理。在这篇综述文章中,我们将介绍一些疫苗流行病学的关键概念
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引用次数: 4
Neoantigen: A New Hope for Effective Cancer Immunotherapy 新抗原:癌症有效免疫治疗的新希望
Pub Date : 2019-12-31 DOI: 10.17140/vroj-4-113
N. Khansari
In recent years, immunotherapy with the aim of augmenting the body's immune system to recognize and destroy tumor cell has been widely investigated as a novel cancer therapy modality. Immune responses can be naturally generated against cancer cells. On the other hand, cancer cells can inhibit anticancer immune responses. In the past decades, vaccination with tumor specific/associated antigens and immunogenic vectors has been successfully used to increase antitumor immune responses. However, the choice of target antigen is imperative in designing a cancer vaccine.
近年来,以增强机体免疫系统识别和破坏肿瘤细胞为目的的免疫治疗作为一种新的癌症治疗方式得到了广泛的研究。免疫反应可以自然产生对抗癌细胞。另一方面,癌细胞可以抑制抗癌免疫反应。在过去的几十年里,用肿瘤特异性/相关抗原和免疫原性载体接种疫苗已成功地用于增强抗肿瘤免疫反应。然而,在设计癌症疫苗时,靶抗原的选择是必不可少的。
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引用次数: 0
Self-Adjuvanting Peptide Vaccines Against Cervical Cancer 预防子宫颈癌的自佐剂肽疫苗
Pub Date : 2019-12-31 DOI: 10.17140/vroj-4-114
Hannah Hanh-Hong Truong, W. M. Hussein, Tzu-yu Liu, Zhongfan Jia, J. Wells, M. Monteiro, M. Skwarczynski
Background Cervical cancer is a common cause of cancer-related deaths in women worldwide, with a fatality rate second only to breast cancer. Human papillomaviruses (HPVs) are the main causative agents of cervical cancer, and are therefore obvious targets for vaccine development. Although two prophylactic HPV vaccines have been commercialized, therapeutic vaccines against HPVs have not been developed yet. Current vaccine technologies emphasize the power of small particles in targeting immune cells, and particles of 20-50 nm have been reported to induce optimal immune responses against a variety of pathogens and cancers. Methods We synthesized new nanoparticle-based vaccines against cervical cancer by using antigenic 8Qmin peptide epitope derived from HPV-16 E7 protein, a hydrophilic poly-(L-glutamic acid) (PGA) linker, and an 8-arm poly (tert-butyl acrylate) dendrimer-based delivery system (D8). Results Four different peptides containing 8Qmin and PGA of different lengths were successfully synthesized with high yield and purity. These were then conjugated to alkyne-functionalized D8 by copper-catalyzed alkyne-azide cycloaddition “click” reaction. The conjugates self-assembled into nanoparticles, with decreased particle size corresponding to a greater number of Glu units. The four vaccine candidates were tested in C57 black 6 (C57BL/6) mice bearing well-established (7-day-old) tumors to examine their therapeutic effects. Conclusion Interestingly, only one conjugate delayed tumor growth, and montanide adjuvanted antigen, used as a positive control, failed to demonstrate any therapeutic effect.
宫颈癌是全世界妇女癌症相关死亡的常见原因,死亡率仅次于乳腺癌。人乳头瘤病毒(hpv)是宫颈癌的主要病原体,因此是疫苗开发的明显目标。虽然两种预防性HPV疫苗已经商业化,但尚未开发出针对HPV的治疗性疫苗。目前的疫苗技术强调小颗粒靶向免疫细胞的能力,据报道,20-50纳米的颗粒可诱导针对多种病原体和癌症的最佳免疫反应。方法利用从hpv - 16e7蛋白衍生的抗原8Qmin肽表位、亲水性聚l -谷氨酸(PGA)连接体和8臂聚丙烯酸叔丁酯树突基递送系统(D8)合成新型宫颈癌纳米颗粒疫苗。结果成功合成了4种不同长度的含8Qmin和PGA的多肽,产率高,纯度高。然后通过铜催化的炔-叠氮环加成“咔嗒”反应将其偶联成炔功能化的D8。共轭物自组装成纳米颗粒,随着Glu单元数量的增加,颗粒尺寸减小。四种候选疫苗在C57黑6 (C57BL/6)小鼠身上进行了测试,这些小鼠的肿瘤已经建立(7天),以检验它们的治疗效果。有趣的是,只有一种偶联物延迟了肿瘤的生长,而montanide佐剂抗原作为阳性对照,没有显示出任何治疗效果。
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引用次数: 2
Consensus Meeting on International Standards for Oral Whole Cell Killed Cholera Vaccines, 17-18 May 2018, Seoul, Republic of Korea 口服全细胞灭活霍乱疫苗国际标准共识会议,2018年5月17日至18日,韩国首尔
Pub Date : 2019-12-31 DOI: 10.17140/vroj-4-112
L. Odevall, SjoerdG. T. Rijpkema, Dean Smith, Tong Wu, F. Qadri, J. Holmgren, J. Lynch, V. Pavliak
Cholera causes an estimated 3 million cases of watery diarrhea and 100,000 deaths globally per year. Although the long-term solution for cholera control lies in universal access to safe drinking water and adequate sanitation, Oral Cholera Vaccines (OCVs) are the most cost-effective measure to contain and prevent the disease and are recommended by the World Health Organization (WHO) as part of an integrated strategy to control cholera. Currently, three OCVs are WHO prequalified and two of these are part of the cholera vaccine stockpile. Other OCVs have been developed for national use or are under development. Lipopolysaccharide (LPS) Inhibition enzyme-linked immunosorbent assays (ELISAs) are used by both manufacturers of OCVs and national regulatory agencies (NRAs) for: in process analysis, as a potency assay for drug substance and drug product batch release, and as an indicator of stability during the shelf life of OCVs. To ensure quality and consistency of this assay performed by different OCV manufacturers and NRAs, harmonization of assay reagents by the introduction of WHO International Standards (IS) for essential reagents is desirable. In May 2018, the International Vaccine Institute (IVI) with assistance from National Institute of Biological Standards and Control (NIBSC) and financial support from the Bill and Melinda Gates Foundation (BMGF) organized a meeting with representatives from vaccine manufacturers, NRAs, leading research institutions and independent experts to discuss and share experiences on potency assays for batch release and select reagents of the LPS Inhibition ELISA as candidate WHO ISs.
据估计,霍乱每年在全球造成300万例水样腹泻和10万人死亡。虽然控制霍乱的长期解决办法在于普遍获得安全饮用水和适当的卫生设施,但口服霍乱疫苗是控制和预防该疾病的最具成本效益的措施,世界卫生组织(世卫组织)建议将其作为控制霍乱综合战略的一部分。目前,有三个ocv通过了世卫组织的资格预审,其中两个是霍乱疫苗储备的一部分。其他ocv已开发供国家使用或正在开发中。脂多糖(LPS)抑制酶联免疫吸附测定法(elisa)被ocv制造商和国家监管机构(NRAs)用于:过程分析,作为原料药和药品批释放的效价测定,以及作为ocv保质期内稳定性的指标。为确保不同OCV制造商和NRAs进行的检测的质量和一致性,需要通过引入世卫组织基本试剂国际标准来统一检测试剂。2018年5月,国际疫苗研究所(IVI)在美国国家生物标准与控制研究所(NIBSC)的协助下,在比尔和梅林达·盖茨基金会(BMGF)的财政支持下,组织了一次会议,与会的有疫苗生产商、美国国家疫苗管理局、主要研究机构和独立专家的代表,讨论和分享了批释放效价测定的经验,并选择了LPS抑制ELISA试剂作为候选世卫组织ISs。
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引用次数: 1
Salmonella-based Anticancer Vaccines and their Efficacy 基于沙门氏菌的抗癌疫苗及其功效
Pub Date : 2019-12-31 DOI: 10.17140/vroj-4-111
S. Farashi-Bonab, N. Khansari
Surgery, chemotherapy, and radiotherapy are successfully used to treat patients with tumors or cancers. However, the innovation of more potent therapeutic modalities is essential for the efficient treatment of patients with advanced cancers. More than two centuries ago, bacteria have been observed to have beneficial effects in some cancer patients. Virulence factors of some bacteria and their infectious behavior in the body suggest their effectiveness in tumor suppression. At present, bacillus calmette-guérin (BCG), a live attenuated strain of Mycobacterium bovis, is currently used to treat bladder cancer. Some other bacteria have also been found to have antitumor activities. Anaerobic bacteria can colonize solid tumors and exert an intrinsic antitumor effect. Salmonella is the most studied bacterium in the field of bacterial anticancer therapy in preclinical studies. In this article, we discuss progress in the development of bacterial anticancer vaccines, especially Salmonella-based vaccines, their antitumor efficacy, and mechanisms involved in vaccine-mediated cancer cell death.
手术、化疗和放射治疗成功地用于治疗肿瘤或癌症患者。然而,创新更有效的治疗方式对于有效治疗晚期癌症患者至关重要。两个多世纪以前,人们就观察到细菌对一些癌症患者有益。一些细菌的毒力因子及其在体内的感染行为表明它们具有抑制肿瘤的作用。目前,卡介苗是牛分枝杆菌的一种减毒活株,用于治疗膀胱癌。其他一些细菌也被发现具有抗肿瘤活性。厌氧菌能在实体瘤中定植,并发挥内在的抗肿瘤作用。沙门氏菌是临床前研究中细菌抗癌治疗领域研究最多的细菌。在这篇文章中,我们讨论了细菌抗癌疫苗,特别是沙门氏菌疫苗的发展进展,它们的抗肿瘤功效,以及疫苗介导的癌细胞死亡机制。
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引用次数: 1
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Vaccination research : open journal
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