Understanding Typhoid Disease After Vaccination: a Single Centre, Randomised, Doubleblind, Placebo Controlled Study to Evaluate M01ZH09 in a Healthy Adult Challenge Model, Using Ty21a Vaccine as a Positive Control.

Using an established model of human typhoid infection, whereby healthy adults are deliberately infected with typhoid-causing bacteria, the investigators will determine how effective a new oral typhoid vaccine (M01ZH09) is in preventing infection. A previously licensed oral typhoid vaccine (Ty21a) will be used to make sure the challenge model used works properly.

开始日期2011-10-07

申办/合作机构

University of Oxford

[+3]

NCT00679172

/ Completed临床2期

A Randomised, Double-blind, Placebo-controlled, Single Dose, Dose Escalation Study to Determine the Immunogenicity, Safety and Tolerability of S. Typhi (Ty2 aroC-ssaV-) ZH9 at Doses of 5.0 x 10E9 CFU, 7.5 x 10E9 CFU, 1.1 x 10E10 and 1.7 x 10E10 CFU and 1.7 x 10E10 CFU, Following Oral Administration to Healthy, Typhoid Vaccine naïve Subjects in the USA.

This study is to investigate the safety, tolerability and immunogenicity of the typhoid fever vaccine candidate M01ZH09 manufactured at commercial scale, at a new manufacturing facility. The vaccine will be delivered as a single oral dose to healthy, typhoid vaccine-naïve adults.

开始日期2008-05-01

申办/合作机构

Emergent BioSolutions, Inc.

ISRCTN45854377

/ CompletedN/A

A placebo controlled single-blind single-dose study to determine the immunogenicity and safety of freeze dried M01ZH09 typhoid vaccine in healthy adult volunteers from Viet Nam

开始日期2005-10-18

申办/合作机构-

100 项与伤寒疫苗(Emergent BioSolutions, Inc.) 相关的临床结果

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100 项与伤寒疫苗(Emergent BioSolutions, Inc.) 相关的专利（医药）

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项与伤寒疫苗(Emergent BioSolutions, Inc.) 相关的文献（医药）

2025-05-01·Redox Biology

Accelerating inflammatory resolution in humans to improve endothelial function and vascular health: Targeting the non-canonical pathway for NO

Article

作者: Kapil, Vikas ; Ono, Mutsumi ; Massimo, Gianmichele ; Khambata, Rayomand S ; Lau, Clement ; Nuredini, Gani ; Hamers, Alexander Jp ; Bin Noorany Aubdool, Muhammad Aadil ; Osman, Miski ; Rathod, Krishnaraj S ; Chhetri, Ismita ; Masucci, Michael ; Primus, Christopher P ; Khan, Zara ; Ahluwalia, Amrita ; Whitear, Charlotte ; Godec, Tom ; Kumar, Nitin Ajit ; Amarin, Julie ; Montalvo Moreira, Shanik A ; Shabbir, Asad

BACKGROUND:

Chronic cardiovascular diseases (CVD) are characterised by low-grade systemic inflammation in part due to reduced nitric oxide (NO) bioavailability associated with endothelial dysfunction. Bioavailability of NO can be enhanced by activation of the non-canonical pathway, through increased dietary inorganic nitrate consumption with the potential to attenuate inflammation.

METHODS:

We sought to determine whether dietary inorganic nitrate influences the inflammatory response in models of localised (cantharidin-induced blisters) and systemic inflammation (typhoid vaccine), in healthy male volunteers and conducted two clinical trials; Blister-NITRATE and Typhoid-NITRATE respectively.

RESULTS:

We show that dietary nitrate attenuates endothelial dysfunction following typhoid vaccine administration and accelerates resolution of cantharidin-induced blisters. Both phenomena were associated with an increased level of pro-resolving mediators consequent to a reduction in the expression and activity of pro-inflammatory monocytes. Moreover, we show that leukocytes of the monocyte lineage express the nitrite reductase XOR, that may drive localised nitrite reduction to elevate NO (and cGMP) to drive the protective phenotype.

CONCLUSIONS:

Inorganic nitrate improves endothelial function in the setting of systemic inflammation. Whilst the immediate inflammatory response appeared unaffected by inorganic nitrate treatment, during the resolution phase of the acute inflammatory response lower levels of pro-inflammatory classical inflammatory and intermediate monocytes and attenuated levels of inflammatory cytokines and chemokines were evident. We propose that this reflects a pro-resolution phenotype that may be of potential therapeutic benefit in patients with established CVD.

CLINICAL TRIAL REGISTRATION:

URL: https://www.

CLINICALTRIALS:

gov; unique identifiers NCT02715635, NCT03183830.

2024-12-31·Expert Review of Vaccines

Lessons from a decade of adult vaccine rollout in low- and middle-income countries: a scoping review

Article

作者: Jerene, Degu ; Gill, Michelle M. ; Buis, Joeri S. ; Pelzer, Puck T. ; DeLuca, Andrea N. ; Georgewill, Onimitein ; Majidulla, Arman ; Limaye, Rupali J. ; Kerkhoff, Andrew D. ; Gerste, Amelia K. ; Baidya, Anurima

INTRODUCTION:

The historical focus of vaccines on child health coupled with the advent of novel vaccines targeting adult populations necessitates exploring strategies for adult vaccine implementation.

AREAS COVERED:

This scoping review extracts insights from the past decade's experiences introducing adult vaccines in low- and middle-income countries. Among 25 papers reviewed, 19 focused on oral cholera vaccine, 2 on Meningococcal A vaccines, 2 on tetanus toxoid vaccine, 1 on typhoid vaccine, and 1 on Ebola vaccine. Aligned with WHO's Global Framework for New TB Vaccines for Adults and Adolescents, our findings center on vaccine availability, accessibility, and acceptance.

EXPERT OPINION:

Availability findings underscore the importance of understanding disease burden for prioritization, multi-sectoral collaboration during planning, and strategic resource allocation and coordination. Accessibility results highlight the benefits of leveraging existing health infrastructure and adequately training healthcare workers, and contextually tailoring vaccine delivery approaches to reach challenging sub-groups like working male adults. Central to fostering acceptance, resonant sensitization, and communication campaigns engaging the communities and utilizing trusted local leaders countered rumors and increased awareness and uptake. As we approach the introduction of a new adult TB vaccine, insights from this review equips decision-makers with key evidence-based recommendations to support successful and equitable vaccinations targeting adults.

2024-11-01·Lancet Global Health

The effect of BCG revaccination on the response to unrelated vaccines in urban Ugandan adolescents (POPVAC C): an open-label, randomised controlled trial

Article

作者: Serubanja, Joel ; van Dam, Govert J ; Webb, Emily L ; Kakande, Ayoub ; Kaleebu, Pontiano ; Natukunda, Agnes ; Kabali, Joel ; Nassuuna, Jacent ; Zirimenya, Ludoviko ; Kukundakwe, Christine ; Kabagenyi, Joyce ; Kiwudhu, Fred ; Nkurunungi, Gyaviira ; Namusobya, Loyce ; Oduru, Gloria ; Mutebe, Alex ; Apule, Barbara ; Kabuubi, Prossy N ; Akello, Florence A ; Sewankambo, Moses ; Kizindo, Robert ; Katushabe, Charity ; Ninsiima, Caroline ; Kizza, Moses ; Nayebare, Doreen ; Walusimbi, Bridgious ; Akello, Mirriam ; Elliott, Alison M ; Kiwanuka, Samuel ; Akurut, Hellen ; Nkangi, Ronald ; Nassanga, Beatrice ; Driciru, Emmanuella ; Kayiwa, John ; Wajja, Anne ; Nankabirwa, Christine ; Onen, Caroline ; Namutebi, Milly ; Amongi, Susan ; Cose, Stephen ; Kabami, Grace ; Nyanzi, Ruth ; Amongin, Rebecca ; Tumusiime, Josephine ; Zziwa, Christopher ; Nakazibwe, Esther ; Tumwesige, Pius ; Nsubuga, Denis ; Corstjens, Paul L A M

BACKGROUND:

Immune responses induced by several important vaccines differ between populations, with reduced responses in low-income and rural settings compared with high-income and urban settings. BCG immunisation boosts immune responses to some unrelated vaccines in high-income populations. We aimed to test the hypothesis that BCG revaccination can enhance responses to unrelated vaccines in Ugandan schoolchildren.

METHODS:

We conducted an open-label, randomised controlled trial to compare the effects of BCG revaccination versus no BCG revaccination on the immunogenicity of subsequent unrelated vaccines among adolescents aged 13-17 years who are participants in an urban Ugandan birth cohort study, in which BCG vaccination was documented at birth. Participants were excluded if they had received any of the trial vaccines or related agents when aged 5 years or older. Computer-generated 1:1 randomisation was implemented in REDCap. Participants were excluded if they were concurrently enrolled in other trials; had a clinically significant history of immunodeficiency, or serious psychiatric conditions or moderate to severe acute illnesses; were taking immunosuppressive medications; had allergies to vaccine components, a predisposition towards developing keloid scarring; positive HIV tests or pregnancy tests; were female participants who were lactating; or if they planned to use investigational drugs, vaccines, blood products, or any combination thereof. Trial participants assigned to the BCG revaccination group received the live parenteral BCG-Russia vaccine (Serum Institute of India, Pune, India; 0·1 mL intradermally, right upper arm) at week 0. All participants received yellow fever vaccine (YF-17D; Sanofi Pasteur, Lyon, France; 0·5 mL intramuscularly, left upper arm), live oral typhoid vaccine (Ty21a; PaxVax, London, UK; one capsule per day taken for three alternate days), and quadrivalent virus-like particle human papillomavirus (HPV) vaccine (Merck, Rahway, NJ, USA; 0·5 mL intramuscularly, left upper arm) at week 4; and toxoid vaccines (tetanus-diphtheria; Serum Institute of India; 0·5 mL intramuscularly, left upper arm) and an HPV booster at week 28. An additional HPV vaccination at week 8 was provided to female participants older than 14 years who had not previously been vaccinated. The primary outcomes were yellow fever neutralising antibody titres at 4 weeks post-YF-17D vaccination, Salmonella enterica serovar Typhi (henceforth S Typhi) O-lipopolysaccharide (O:LPS)-specific IgG concentration at 4 weeks post-Ty21a vaccination, and HPV-16 and HPV-18 L1 protein-specific IgG concentration at 4 weeks post-HPV vaccination. Primary outcome assays were conducted at week 8, and at week 52 for tetanus-diphtheria. We conducted an intention-to-treat analysis comparing log-transformed outcomes between trial groups, with results back-transformed to geometric mean ratios (GMRs). The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN10482904) and is complete.

FINDINGS:

Between Aug 31 and Oct 12, 2020, we screened 376 potential participants for eligibility. We enrolled and randomly allocated 300 participants to the two groups (151 [50%] to the BCG group and 149 [50%] to the no BCG group). 178 (59%) of 300 participants were male and 122 (41%) were female. 142 (91%) of 151 participants in the BCG group and 139 (93%) of 149 in the no BCG group completed follow-up. There was no effect of BCG revaccination, compared with no BCG revaccination, on the response observed for any vaccine. Yellow fever plaque reduction neutralising reference tests (PRNT₅₀) titres (the reciprocal of the last plasma dilution that reduced by 50%) had a GMR of 0·95 (95% CI 0·75-1·19; p=0·62) and PRNT₉₀ (reciprocal of the last plasma dilution that reduced by 90%) had a GMR of 0·94 (0·74-1·19; p=0·60); IgG to S Typhi O:LPS was 0·99 (0·80-1·23; p=0·94); IgG to HPV-16 was 0·97 (0·69-1·35; p=0·85) and to HPV-18 was 1·03 (0·76-1·40; p=0·83); and toxoid-specific IgG for tetanus was 1·13 (0·87-1·47; p=0·36) and was 1·00 (0·87-1·16; p=0·97) for diphtheria. There were no serious adverse events in either group.

INTERPRETATION:

We found no evidence that BCG revaccination is an effective strategy to improve immunogenicity of other vaccines in this low-income, urban setting.

FUNDING:

UK Medical Research Council.

TRANSLATION:

For the Luganda translation of the abstract see Supplementary Materials section.

项与伤寒疫苗(Emergent BioSolutions, Inc.) 相关的新闻（医药）

2025-02-16

·药明康德

打这些常见疫苗有望降低痴呆症风险？

▎药明康德内容团队编辑痴呆症作为全球性的重大健康挑战，不仅给患者及其家庭带来了沉重的身心负担，也对全球公共卫生构成了巨大的压力。近年来，越来越多的研究表明，某些病毒感染可能与痴呆症的风险增加相关，而接种相应的疫苗则可能降低痴呆症的发病风险。在今天的文章里，药明康德内容团队将结合最新研究结果，深入探讨疫苗接种与痴呆症之间的关联。常规疫苗接种或可降低阿尔茨海默病风险？早在2023年，科学家们就发现，接种过破伤风和白喉疫苗（Tdap/Td，伴或不伴百日咳疫苗）、带状疱疹疫苗或肺炎球菌疫苗的成年人，其罹患阿尔茨海默病（AD）的风险显著低于未接种者。具体而言，在65岁及以上人群中，接种Tdap/Td后AD风险降低30%，接种带状疱疹疫苗后AD风险降低25%，接种肺炎球菌疫苗后AD风险降低27%。此外，该研究团队此前还发现，接种流感疫苗的人群患AD的风险比未接种者低40%。除了上述研究，其他研究也揭示了疫苗接种与痴呆症风险降低之间的关联。例如，今年1月，英国剑桥大学的研究团队分析了1.3亿人的健康数据，其中包括100万名确诊为痴呆症的患者。他们发现，接种以下四种疫苗与痴呆症风险降低有关：甲型肝炎疫苗、伤寒疫苗、联合甲型肝炎和伤寒疫苗，以及白喉疫苗。此外，这项研究还指出，抗生素、抗病毒药物和抗炎药物均与痴呆症风险降低有关。这些研究结果表明，疫苗不仅能在短期内预防传染病，还可能通过调节免疫系统对神经退行性疾病产生长期保护作用。这些发现不仅拓展了疫苗的应用价值，也为痴呆症的预防提供了新的科学依据。病毒感染与神经退行性疾病的关联越来越多的研究揭示了常见病毒感染与神经退行性疾病之间的潜在联系，这些病毒感染在体内引发的长期炎症反应，当波及大脑时，可能触发一系列化学反应，导致脑细胞损伤及其相互通信能力受损，从而为痴呆症的发生奠定病理基础。鉴于此，通过疫苗接种来预防和减轻病毒或细菌感染的严重程度，有望减少大脑炎症的发生，进而降低神经退行性疾病的风险。 2023年的一项研究揭示了甲型流感病毒感染对神经系统的潜在危害。研究发现，甲型流感病毒可能导致神经元突触的关键结构——树突棘的丢失，进而损害海马区突触的可塑性，并显著影响空间记忆的形成。研究作者指出，疫苗接种可能是预防这些神经病理学改变的有效策略。进一步的研究表明，某些甲型流感病毒亚型（如H7N7）能够侵入中枢神经系统并在脑细胞内复制，从而引发小胶质细胞介导的神经炎症反应，最终导致神经元损伤。该研究还发现，灭活H7N7疫苗在预防病毒感染后外周和中枢神经系统的炎症反应方面具有显著效果。具体而言，疫苗接种显著降低了H7N7感染后细胞因子和趋化因子的水平，减少小胶质细胞的密度并抑制其体积增大。此外，疫苗还成功防止了树突棘的丢失，研究人员推测这一保护作用可能是通过调节小胶质细胞对突触后成分的吞噬过程来实现的。显著的认知功能障碍也在COVID后遗症（long COVID）患者中被观察到。2025年1月的一项研究显示，曾经感染过COVID-19的人群更有可能出现大脑中与错误折叠的淀粉样蛋白相关的生物标志物水平升高，而淀粉样蛋白的积累正是阿尔茨海默病的标志性病理特征之一。科学家们指出，即使是轻度或中度的COVID-19感染，也可能加速大脑中淀粉样蛋白积累的生物学进程。此外，2022年的一项研究通过对超过600万人群的医疗数据进行分析发现，65岁及以上感染COVID-19的人群在一年内确诊为阿尔茨海默病的风险增加了近70%。这些发现提示，COVID-19感染可能通过多种机制增加罹患神经退行性疾病的风险。除了上述呼吸道病毒之外，研究还发现疱疹病毒也可能增加感染后罹患阿尔茨海默病和痴呆症的风险。例如，一些回顾性研究的结果表明，与血清阴性个体相比，单纯疱疹病毒1型（HSV-1）血清阳性者的痴呆风险显著更高，且抗病毒治疗可显著降低后续痴呆的发生率。此外，带状疱疹眼病患者的痴呆症发病率也高于无此病症的对照组。一些研究为HSV-1感染与AD的发生相关性提供了直接证据。既往研究已证明，溶酶体功能障碍会促进神经退行性病变的发展，而神经元尤其容易受到溶酶体损伤的影响。有研究发现，细胞培养中，HSV-1感染与氧化应激会加重溶酶体负荷并损害其功能，具体表现为水解酶和组织蛋白酶活性降低，同时氧化应激还会影响组织蛋白酶的成熟。这些溶酶体相关的变化在AD早期发展中即可观察到，导致细胞无法有效清除有毒物质，从而进一步解释了HSV-1在AD发病中的作用。图片来源：123RF 此外，还有研究显示，AD患者大脑中人类疱疹病毒6A型和7型（HHV6、HHV7）的水平显著高于对照组，且这些病毒的水平与临床痴呆评分、神经纤维缠结密度以及淀粉样斑块密度等相关。感染这些病毒会导致多种转录调控因子的变化，包括一些调控淀粉样前体蛋白（APP）加工和AD风险相关基因表达的调控因子。这表明病毒水平与各种AD特征性病理变化水平之间密切相关。另有研究发现，注射带状疱疹疫苗与痴呆症发生率的降低相关联，这进一步支持了疫苗接种在预防神经退行性疾病中的潜在作用。扩展阅读：颠覆认知！这种潜伏在老年人体内的病毒，竟可引发阿尔茨海默病？新发现：打了这种疫苗，老年痴呆症发生延缓了综上所述，通过疫苗接种预防病毒感染，不仅能够有效减轻短期内的疾病负担，还有望对长期的神经系统健康产生积极影响。然而，值得注意的是，目前的研究结果大多基于大规模人群医疗数据的分析，这些研究虽然具有重要的启示性，但无法直接确立疫苗接种与降低AD等神经退行性疾病发生风险之间的直接因果联系。因此，未来的研究需要进一步探索这些病毒的具体致病机制，明确疫苗接种与神经退行性疾病风险降低之间的内在联系，并开展随机对照临床试验进行验证。这不仅有助于更有效地应对日益增长的神经退行性疾病负担，更将为社会大众带来福祉。我们期待通过科学家与医护人员持续的努力，能够为神经退行性疾病的预防和治疗提供更加坚实的科学基础，改善全球公共卫生水平。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料： [1] Routine vaccines could prevent dementia– here's how，Retrieved Feb 12, 2025 from https://www.gavi.org/vaccineswork/routine-vaccines-could-prevent-dementia-heres-how [2] Harris, Kristofer et al. ‘The Impact of Routine Vaccinations on Alzheimer’s Disease Risk in Persons 65 Years and Older: A Claims-Based Cohort Study Using Propensity Score Matching’. 1 Jan. 2023 : 703 – 718. [3] Underwood, Benjamin R et al. “Data-driven discovery of associations between prescribed drugs and dementia risk: A systematic review.” Alzheimer's & dementia (New York, N. Y.) vol. 11,1 e70037. 21 Jan. 2025, doi:10.1002/trc2.70037 [4] Demuth, Luisa et al. “Influenza vaccine is able to prevent neuroinflammation triggered by H7N7 IAV infection.” Frontiers in pharmacology vol. 14 1142639. 29 Mar. 2023, doi:10.3389/fphar.2023.1142639 [5] Duff, E.P., Zetterberg, H., Heslegrave, A. et al. Plasma proteomic evidence for increased β-amyloid pathology after SARS-CoV-2 infection. Nat Med (2025). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41591-024-03426-4 [6] Wang, Lindsey et al. “Association of COVID-19 with New-Onset Alzheimer's Disease.” Journal of Alzheimer's disease : JAD vol. 89,2 (2022): 411-414. doi:10.3233/JAD-220717 [7] Itzhaki, Ruth F. “Corroboration of a Major Role for Herpes Simplex Virus Type 1 in Alzheimer's Disease.” Frontiers in aging neuroscience vol. 10 324. 19 Oct. 2018, doi:10.3389/fnagi.2018.00324 [8] Tsai, Ming-Chieh et al. “Increased risk of dementia following herpes zoster ophthalmicus.” PloS one vol. 12,11 e0188490. 22 Nov. 2017, doi:10.1371/journal.pone.0188490 [9] Eyting M, Xie M, Heß S, Geldsetzer P. Causal evidence that herpes zoster vaccination prevents a proportion of dementia cases. medRxiv [Preprint]. 2023 May 25:2023.05.23.23290253. doi: 10.1101/2023.05.23.23290253. PMID: 37292746; PMCID: PMC10246135. 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

疫苗

2024-04-06

·生物制品圈

疫苗的“前世今生”，一段波澜壮阔的历史

疫苗一词是“疫苗之父”巴斯德( Louis Pasteur) 为纪念先驱者琴纳( Edward Jenner) 发明牛痘苗( vaccine) 而创造，指由减毒或灭活微生物制成、能够针对疾病产生免疫力的生物制品。疫苗作为人类与疾病斗争的有力武器，消灭或控制了许多传染病。脊髓灰质炎、鼠疫、麻疹、狂犬病、百日咳、破伤风、乙型病毒性肝炎(乙肝) 等发病率也通过接种疫苗大幅降低。自 18 世纪天花疫苗诞生至今，疫苗研发经历了数百年的发展其技术发展经历了 3 次革命。第一次始于 19 世纪末，巴斯德研制成功鸡霍乱疫苗、羊炭疽疫苗和狂犬疫苗，并利用生物传代和物理化学方法处理病原体，得到减毒和灭活疫苗; 第二次发生在 20 世纪 80 年代，其标志是以酵母制造乙肝疫苗。这一阶段，以重组 DNA 技术为代表的分子生物学技术的发展，使疫苗的研究从整体病原体水平进阶到分子水平; 第三次是 20 世纪 90 年代研制成功核酸疫苗，该技术最早由美国的沃夫( Wolff) 等发明。人类使用疫苗预防疾病已有200多年的历史，疫苗作为人类与疾病斗争的有力武器，消灭或控制了许多传染病。今天我们就来回顾一下，疫苗经历了怎样的发展轨迹？疫苗发展历程梳理一、萌芽期疫苗的横空出世首先得从天花病毒说起。天花是一种烈性传染病，不论什么人，一旦与患者接触，几乎都会传染，并且死亡率极高。但是在长时间的医疗中发现，有两种人是对天花有抵抗力的：一是从天花中康复的人，二是曾经护理过天花病的人。我们的前人在这种现象的启发下，研究出了用人痘接种预防天花的方法。该方法是将沾有疤浆患者的衣服给正常儿童穿戴，或将天花愈合后局部皮肤组织研磨成细粉，经鼻使儿童吸入。我们的前人在这种现象的启发下，研究出了用人痘接种预防天花的方法。该方法是将沾有疤浆患者的衣服给正常儿童穿戴，或将天花愈合后局部皮肤组织研磨成细粉，经鼻使儿童吸入。不过因为风险太大，这个技术一直没有推广开来，但这个技术的发展却给了人们很大的启发，让他们找到了对抗天花的方法。在18世纪末，一名英国的乡下大夫爱德华-琴纳接待一名妇女，她患有发烧、腰疼、呕吐等症状，他从中意识到接种牛痘可以预防天花。为了证实这一设想，他于1796年5月14日从一名正患牛痘的挤奶女工身上的脓疤里取少量脓液注射至八岁男孩詹姆斯费普臂内。六周后，男孩的牛痘反应消退，所以正如琴纳所说：“尽管假性天花接种小孩手臂出现类似的脓疤，除此之外几乎不可觉察。”琴纳为了证实其效果，先后多次给费普接种，但费普却安然无恙。2个月后，再接种天花患者来源的痘液，费普仅局部手臂出现疤疹，未引起全身天花。据此，琴纳于1798年出版其专著《探究》，称此技术为疫苗接种。在琴纳那个时代，人们根本不知道天花是由一种病毒引起的，也不知道种痘能让身体产生一种对抗天花的免疫。但是，经过他的实际观察，经过试验，确定了一种新的疫苗接种法，它不仅安全，而且很有效，是一个划时代的发明。琴纳（公元1749年—公元1823年）二、第一次疫苗革命这一阶段疫苗的发展归功于路易·巴斯德于19世纪末在疫苗研制领域的先锋作用和卓越贡献。被誉为疫苗之父的巴斯德的伟大贡献在于：他选用免疫原性强的病原微生物经培养，用物理或化学方法将其灭活后，再经纯化制成。灭活疫苗使用的毒种一般是强毒株，但使用减毒的弱毒株也有良好的免疫原性，如用萨宾减毒株生产的脊髓灰质炎灭活疫苗。减毒活疫苗是采用人工定向变异的方法，或从自然界筛选出毒力高度减弱或基本无毒的活的微生物制成疫苗，并以此给人接种而达到预防传染病的目的。在19世纪末，科赫发明了在固体培养基上分离细菌培养物的方法，该法为巴斯德研制疫苗奠定了基础。巴斯德首次发现，长期在人工培养基上，如将鸡霍乱弧菌置于两个星期后，这种菌种对雏鸡不会造成致病性。还有一点很重要：即使再次给这些被注射过的雏鸡注射了霍乱，他们也不会感染。巴斯德提出，这可能是因为在老的培养基中，鸡霍乱弧菌的毒性降低，但是其免疫原性保持不变，从而导致雏鸡对霍乱弧菌有了免疫力。以此理论巴斯德将炭疽杆菌在42~43℃的环境下培养两周后，制成人工减毒炭疽活疫苗。在巴斯德光辉成就的启发下，1908年卡麦特和古林将一株牛型结核杆菌在含有胆汁的培养基上连续培养13年213代，终于在1921获得减毒的卡介苗(BCG)。最初卡介苗为口服，20世纪20年代末改为皮内注射，卡介苗在新生儿抵御粟粒性肺结核和结核性脑膜炎方面具有很好的效果。自1928年至今，卡介苗仍在全世界广泛地被用于儿童计划免疫接种，已有40多亿人接种过卡介苗。这一阶段疫苗革命中还包括白喉、破伤风类毒素、鼠疫疫苗、伤寒疫苗和黄热病等30多种疫苗的成功研制。巴斯德三、第二次疫苗革命第二次疫苗革命主要是从分子水平上制备基因工程亚单位疫苗。由于分子生物技术、生物化学、遗传学和免疫学的迅速发展，使得研制新疫苗和改进旧疫苗的工作能够在分子水平上进行。以酵母制备乙肝疫苗作为二次疫苗革命的分水岭。采用重组DNA技术、蛋白质化学技术开创了疫苗研制的第二次革命。1.重组核酸技术美国斯坦福大学于1972年提出重组核酸技术，并以迅雷不及掩耳之势风靡世界，开创了生命科学的新局面，其中包括疫苗的研制。基因重组技术的运用，为疫苗的研发提供了一条崭新的道路。该技术不仅可以获得几乎所有的免疫原，还可以让病原微生物的研究者和疫苗的接种者变得更加安全。例如，乙肝疫苗最初是从人乙型肝炎表面抗原(HBsAg)携带者血浆中提取，对健康人来说，其接种的危险性显而易见。20世纪80年代，又有研究报道了 HBsAg的基因在酵母和真核细胞中的表达，该方法既可获得类似于血液疫苗的免疫效果，又可获得简单、快速、廉价、高效的 HBsAg的抗体，对接种人群具有较高的安全性。当前，在不改变疫苗抗原性的前提下，利用重组核酸技术，以病毒、细菌作为载体，将目标基因导入到疫苗菌株及其质粒的基因组中，从而在不改变其抗原性的情况下，实现对疫苗菌株的高表达。所以，该疫苗对人体所起到的免疫作用是双向的。例如，第一次疫苗革命产生的卡介苗，现在采用重组核酸技术将γ-干扰素(IFN-γ)、白细胞介素2(IL-2)等细胞因子基因导入卡介苗中，成为重组卡介苗(γBCG)。重组卡介苗不仅保留传统卡介苗的特性，同时还分泌γ-干扰素和白细胞介素2，这样重组卡介苗既可用于结核病的预防，又能用于肿瘤或其他免疫性疾病的治疗。2.蛋白质化学和化学技术由于疫苗中的保护性抗原大部分为蛋白质，所以要得到特异性的蛋白质抗原，必须先对其进行分离纯化，由此可见蛋白质化学技术的发展对疫苗的研制起着重大作用。另外，可根据骨髓依赖性(B)淋巴细胞表位或胸腺依赖性(T)淋巴细胞表位直接采用蛋白质化学和化学技术合成多肤抗原，用来制备多肤疫苗。四、第三次疫苗革命核酸疫苗的开发研制，标志着第三次疫苗革命的到来。1995年美国纽约科学院召开专门研讨核酸疫苗会议，称之为疫苗学的新纪元和疫苗的第三次革命。1.核酸疫苗的发现和研制沃夫等人偶然的研究成果以及阿瑟的基因递送体系，为发展新型核酸疫苗奠定了基础。20世纪80年代后期，90年代初期，人们利用表达基因的核酸进行基因疗法，发现不经任何处理的裸露基因，可以在肌肉细胞内表达蛋白质，并且可以在肌肉细胞内持续两个月，引起人体产生免疫反应，由此引发了一场核酸疫苗的研发。在最初的动物实验中有两个令人欣喜的结果:第一是A型流感病毒核酸疫苗注射给小鼠，结果诱发了小鼠产生抗体和细胞毒性T细胞。然后用A型流感(PR/8) 攻击，100%小鼠健康存活，而对照组100%在9天后死亡。几乎同时，费南(Fynan)等人使用基因枪和编码红细胞凝集素的核酸，其结果也使小鼠获得保护性免疫应答。另一个重要的研究结果是乙肝表面抗原的核酸疫苗。该疫苗不但能诱导动物产生相应的抗体，还能让转基因动物体内的 HBV表面抗原呈阴性。因此，可以用核酸疫苗来预防和治疗疾病，特别是对乙型肝炎的核酸疫苗。该结果对目前国内乙型肝炎疫苗的研发具有一定的指导意义。2.核酸疫苗的应用前景核酸疫苗的研究进展令人鼓舞，核酸疫苗因其独特的优势，在免疫防治中发挥了重要作用。因此，自1994年以来，美国 FDA先后批准了包括 AIDS，流感，乙肝，单纯疤疹，疟疾，Cancer在内的几种核酸疫苗的临床试验。欧美各国都投入了大量的人力物力，对核酸疫苗进行了研发。核酸疫苗已用于淋巴瘤、黑色素瘤、结肠癌及前列腺癌的临床前治疗研究。据统计，1989年至2004年，全球得到认可的基因治疗临床试验共9987例，仅肿瘤治疗占66%。然而，由于其高致死率，迄今尚无针对肝癌 DNA疫苗进行临床研究的相关报道。因此，开展肝癌核酸疫苗临床应用的研究具有重要意义。核酸疫苗也被广泛应用于基因缺陷导致的免疫缺陷疾病的治疗，其中以 ADA基因为代表的基因治疗是目前最有效的一种。mRNA 疫苗技术在新冠疫情应对中市场前景得到较大提升。2020年是 mRNA 技术平台的突破元年，新冠 mRNA 疫苗的推出和广泛使用极大提升了mRNA 疫苗的融资和市场活力。目前开发中的 mRNA 制剂有3个主要应用：预防性疫苗、治疗性疫苗和治疗药物。复星与拜恩泰科研发的mRNA新冠疫苗样品人类在200多年前就开始应用疫苗，它为我们构筑了一道强有力的生物屏障，使我们免受病毒的攻击。在这次疫情之后，疫苗是人类的“保护神”，这一点是毋庸置疑的。随着技术的进步，经过科学家们的不懈努力，将会有更多的治疗性和预防性疫苗被研制出来。疫苗对于人体的作用，无论怎样夸张也不为过，因为每一种新型疫苗的出现，都代表着一场人类对某种疾病的胜利！参考：[1]许丽丽,陈艳,陈征宇等.疫苗的发展与创新：从天花疫苗到新型冠状病毒疫苗[J].医药导报,2021,40(07):876-881.[2]贾冰冰,李卫国.疫苗技术发展的历史与展望[J].生物学通报,2016,51(06):1-3.[3]https://www.nobelprize.org/prizes/lists/all-nobel-prizes/[4]https://www-nature-com.libproxy1.nus.edu.sg/immersive/d42859-020-00005-8/index.html识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

疫苗

2024-02-15

·Science Daily

Environmental monitoring offers low-cost tool for typhoid fever surveillance

Researchers can accurately track where typhoid fever cases are highest by monitoring environmental samples for viruses called bacteriophages that specifically infect the bacterium that causes typhoid fever. Researchers can accurately track where typhoid fever cases are highest by monitoring environmental samples for viruses called bacteriophages that specifically infect the bacterium that causes typhoid fever. Senjuti Saha of the Child Health Research Foundation in Bangladesh and colleagues report these findings in a new study published February 15 in the open access journal PLOS Neglected Tropical Diseases. Typhoid fever is a common infection in many low- and middle-income countries and causes an estimated 135,000 deaths and 14 million infections globally each year. The World Health Organization has prequalified two typhoid vaccines, but for policymakers to plan effective vaccination strategies, they need accurate, high-resolution estimates of where the burden is highest. Traditionally, people have cultured the bacterium that causes typhoid fever from blood samples to determine where the infection is most common, but in the new paper, researchers tried a more cost-effective surveillance approach. They tested environmental water samples from sewage and other locations to detect bacteriophages specific to the water-borne pathogen that causes typhoid fever, Salmonella Typhi. The team tested 303 water samples from two locations in Bangladesh: the urban capital city, Dhaka, and a rural district, Mirzapur. They found that bacteriophages specific for Salmonella Typhi were present in 31% of environmental samples in Dhaka, compared to just 3% of samples from Mirzapur. This corresponds to results from more than 8,400 blood cultures, in which 5% of cultures from Dhaka and 0.05% from Mirzapur tested positive. The new results suggest that detecting bacteriophages specific for Salmonella Typhi may be a rapid environmental surveillance method that could help decision makers understand the presence of typhoid fever in the community. The researchers propose that environment monitoring of bacteriophage could be a simple, cost-effective and scalable tool to assist policy decisions on typhoid control. The authors add: ""Looking for bacteriophages in wastewater is a low-cost method for identifying typhoid hotspots without doing expensive blood cultures on thousands of people."

疫苗临床结果临床研究

100 项与伤寒疫苗(Emergent BioSolutions, Inc.) 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D06261	-	-	-

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
伤寒	临床2期	美国	Emergent BioSolutions, Inc.	2008-05-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00679172 (CTgov)	临床2期	伤寒	187	Placebo (Cohorts 1-4 pooled)+Dose of 5.0 x 10^9 CFU (Cohort 1) (M01ZH09 Vaccine Candidate Cohort 1)	築鏇鹽網網蓋鏇繭憲淵 = 鹽齋壓鹽鹽窪獵築鏇鹽憲顧鑰艱窪齋窪觸觸遞 (鏇獵襯壓夢艱糧築築夢, 鏇願淵積鏇艱鬱簾醖選 ~ 醖餘憲夢醖醖醖製襯壓) 更多	-	2017-06-07
NCT00679172 (CTgov)	临床2期	伤寒	187	Placebo (Cohorts 1-4 pooled)+Dose of 7.5 x 10^9 CFU (Cohort 2) (M01ZH09 Vaccine Candidate Cohort 2)	築鏇鹽網網蓋鏇繭憲淵 = 廠糧廠簾範鏇廠鏇餘餘憲顧鑰艱窪齋窪觸觸遞 (鏇獵襯壓夢艱糧築築夢, 憲鬱憲鹽憲築廠鏇壓壓 ~ 製憲壓鏇簾鬱醖製蓋製) 更多	-	2017-06-07
NCT00679172 (Pubmed \| Vaccine)	临床2期	伤寒	187	M01ZH09	憲願鏇齋構繭淵鬱製夢(鹽顧衊襯築鏇壓壓築製) = One subject had a transient low-grade fever 遞範遞築鏇糧夢艱鹽築 (遞選淵獵淵齋夢鏇糧窪 )	-	2010-04-30