mRNA疫苗技术概述及新型冠状病毒肺炎mRNA疫苗的研究进展

mRNA疫苗技术的发展受到分子本身不稳定、自身免疫原性高以及体内递送效率低等因素的限制,经过30多年的研究,近年来随着其稳定性、高效传递系统方面的技术日趋成熟,肿瘤和传染病mRNA疫苗研究进展明显。与传统疫苗技术相比,该技术可诱导机体产生体液免疫和细胞免疫,疫苗生产工艺简单、研发周期短、成本低,便于标准化生产,适用于大流行疾病和传染病暴发流行期间的疫苗开发和生产,是一种应用前景广阔的疫苗。在当前新型冠状病毒肺炎全球大流行的背景下,本文从mRNA疫苗的特征、疫苗递送系统入手,结合新型冠状病毒肺炎mRNA疫苗的研究现状进行了分析和阐述,以期为后续的mRNA疫苗研究开发提供参考依据。     

我国新冠疫苗研制生产的监管特点分析

目的:在我国新冠疫苗研制与生产进程加速的背景下,为加强相应的监督管理提供建议.方法:通过查阅文献和公开信息,以及调研,梳理了国内外新冠疫苗的研制、生产与监管的现状.结果 与结论:为应对新冠疫情的流行,我国加快了新冠疫苗的研制和生产进程,对此,我国药品监督管理部门与其他相关部门为保证疫苗质量和保障疫苗供应,在可供借鉴的监...     

Covid-19 Vaccine Surveillance in Saudi Arabia: Opportunities for Real-time Assessment

After months of confronting COVID-19 pandemic, several countries, including Saudi Arabia, have recently approved newly developed vaccines to prevent COVID-19 infection. With the new technology utilized to develop some vaccines, questions arise about their long-term safety. To provide rapid response to emerging safety issues, robust surveillance programs that provide near real-time analysis of vaccines effects are required. Saudi Arabia has a well-established passive pharmacovigilance system that monitors drugs and vaccines safety. However, recent development in health digitalization in Saudi Arabia may provide a unique opportunity to harvest existing resources to generate high-quality evidence. This commentary provides an overview of the available systems that can be utilized to monitor the COVID-19 vaccines’ safety and discusses opportunities for data integration to improve data quality and generate real-world evidence on COVID-19 vaccine safety.     

基于组合赋权-TOPSIS的中国新冠疫苗专利竞争力分析

目的 依据专利数据探究中国主要新冠疫苗技术的发展水平和竞争情况。方法 对中国5种主要新冠疫苗进行专利竞争力评价指标体系的构建,并依据检索到的专利数据进行层次分析法-熵权法组合赋权和TOPSIS竞争力分析。结果 中国现有的5种主要新冠疫苗中,重组亚单位疫苗、重组病毒载体疫苗和核酸疫苗专利竞争力相对较强,灭活疫苗和减毒疫苗相对较弱。结论 中国新冠疫苗专利市场和技术格局逐渐趋于成熟,研发机构应当在确保疫苗安全性的基础上聚焦技术热点、致力创新研发,探索技术发展新出路。     

肺力咳合剂联合莫西沙星治疗慢性阻塞性肺疾病急性加重期的临床研究

目的 探讨肺力咳合剂联合莫西沙星治疗慢性阻塞性肺疾病急性加重期(AECOPD)的临床效果.方法 选取2017年3月—2019年12月天津市第五中心医院收治的116例AECOPD患者,随机分成对照组(58例)和治疗组(58例).对照组静脉滴注盐酸莫西沙星注射液,0.4 g/次,1次/d.治疗组在对照组基础上口服肺力咳合剂...     

Mucosal delivery of nanovaccine strategy against COVID-19 and its variants

Despite the global administration of approved COVID-19 vaccines (e.g., ChAdOx1 nCoV-19®, mRNA-1273®, BNT162b2®), the number of infections and fatalities continue to rise at an alarming rate because of the new variants such as Omicron and its subvariants. Including COVID-19 vaccines that are licensed for human use, most of the vaccines that are currently in clinical trials are administered via parenteral route. However, it has been proven that the parenteral vaccines do not induce localized immunity in the upper respiratory mucosal surface, and administration of the currently approved vaccines does not necessarily lead to sterilizing immunity. This further supports the necessity of a mucosal vaccine that blocks the main entrance route of COVID-19: nasal and oral mucosal surfaces. Understanding the mechanism of immune regulation of M cells and dendritic cells and targeting them can be another promising approach for the successful stimulation of the mucosal immune system. This paper reviews the basic mechanisms of the mucosal immunity elicited by mucosal vaccines and summarizes the practical aspects and challenges of nanotechnology-based vaccine platform development, as well as ligand hybrid nanoparticles as potentially effective target delivery agents for mucosal vaccines.     

Current COVID-19 vaccine candidates: Implications in the Saudi population

AimThe purpose of this review is to discuss the current status of local and international efforts undergoing clinical trials aiming at developing a Coronavirus Disease-2019 (COVID-19) vaccine, and to highlight the anticipated challenges of this vaccine globally and in Saudi Arabia.Present FindingsCOVID-19 vaccine development efforts started in early January 2020 when Chinese scientists shared the Coronavirus genomic sequence in public domain. Approximately 321 research groups initiated the search for a vaccine, out of which 41 have reached phase I/II trails and 11 reached phase-III clinical trials, including approved vaccines for early to limited use. Out of these projects are two labs in the Kingdom of Saudi Arabia still in early stages of development of a COVID-19 vaccine. Several vaccine attempts are being tested from traditional, attenuated virus methods, to new nucleic acid-based designs. However, no vaccine has yet completed clinical trials and reached public domain.In spite of the challenges faced during previous vaccine trials, researchers have found that Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 is structurally similar to the (SARS-CoV-1) and the Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV), which caused epidemics in 2003 and 2012 respectively. Both SARS strains show identical affinity towards the type-II alveolar pneumocytes angiotensin converting enzyme-2 (ACE-2) receptor binding domains and therefore, similar pathogenicity. The race to develop the vaccine is predominantly for individuals at high risk of developing the infection, i.e. population groups who are most susceptible to experiencing fatal symptoms of the coronavirus. These include patients with comorbidities, above the age of 60 years and people at risk of contracting large viral loads, such as healthcare providers caring for critical admissions in in-patient wards, Intensive Care Units and Emergency Room settings.SummaryMany different vaccine strategies are under development throughout different stages of the research timeline; however, it is estimated that none will show favorable results before end of 2020. For any immunization or interventional prevention/therapy system to reach the public and patients at high risk, it needs to undergo multiple phase trials to ensure safety and effectiveness. In this scoping review we aim to map the literature on COVID-19 vaccines and provide recommendations related to gaps in research, applicability and expected challenges for implementation of nationwide vaccination in Saudi Arabia.     

Obstacles and Policy Measures Toward COVID-19 Vaccination: Creating a Sustainable Road Map for Malawi

The Coronavirus Disease 2019 (COVID-19) pandemic is a public health threat for Malawi which is facing several challenges concurrently including disease burden; inadequate finances; illiteracy; and public mistrust in government. In this pandemic, vaccines are the most reliable and cost-effective public health intervention, and the Malawian government has instituted an action plan which includes prioritizing the vaccination of traditional and religious leaders, increased vaccination sites to include workplaces and shopping malls, and health promotion. However, there is still considerable hesitancy around the use of the available vaccines in Malawi. In this paper, we explore the multiple interrelated factors driving COVID-19 vaccine hesitancy in Malawi. It is therefore recommended that the Malawian government embrace multicomponent and wide-ranging strategies to address COVID-19 vaccine hesitancy in the country. This includes reviving trust in national health authorities by offering population-specific, target-driven, and effective, transparent, and timely communication to its citizens and relevant stakeholders about the safety and efficacy of the COVID-19 vaccine.     

Perceptions and predictors of intention to receive the COVID-19 vaccine

BackgroundThe control of the Coronavirus Disease 2019 (COVID-19) pandemic may be dependent on widespread receipt of an effective vaccine. It is important to understand patient health-related behaviors and perceptions to guide public health vaccination strategies.ObjectivesTo examine perceptions of COVID-19 and vaccination beliefs, and identify predictors of intention to receive the COVID-19 vaccine in the US.MethodsA cross-sectional, web-based survey guided by the Health Belief Model was conducted using a web-based Qualtrics survey panel of US adults. The main outcome was the intention to receive the COVID-19 vaccine if offered. Additional measures included: demographics, perceptions of COVID-19 severity, risk and susceptibility, views of a potential COVID-19 vaccine, virus and vaccine information sources, vaccine beliefs and behaviors, and seasonal flu vaccine history.ResultsA total of 1047 complete responses were included. Females had lower odds of intending to receive the COVID-19 vaccine than males (AOR = 0.54, 95% CI: 0.36–0.80). Those with a two-year degree/some college had lower odds of intending to receive the COVID-19 vaccine compared to those with a high school degree/GED (AOR = 0.59, 95% CI: 0.36–0.97). Respondents who perceived the severity of the virus to be higher, perceived a greater COVID-19 vaccine benefit, and perceived greater general vaccine benefits had higher odds of intending to receive a COVID-19 vaccine (AOR = 1.44, 95% CI: 1.09–1.91; AOR = 2.82, 95% CI: 2.24–3.56; AOR = 1.77, 95% CI 1.41–2.21, respectively).ConclusionsIn this study, intention to receive the COVID-19 vaccine varied across demographics, perceived virus severity, COVID-19 vaccine and general vaccine beliefs. Successful implementation of a COVID-19 immunization strategy by healthcare providers and public health officials will need to incorporate diverse COVID-19 vaccination education strategies tailored to patients' health beliefs.     

Willingness of Middle Eastern public to receive COVID-19 vaccines

BackgroundCOVID-19 is a pacing pandemic that affected health systems, economy, and social life in the whole world. Currently, there is no treatment for it, but the world is in a race that yielded, in a relatively short time than usual, several approved, promising vaccines in the middle of a storm of debates because of the speed of their production and approval.ObjectiveThis study assessed the willingness of Middle Eastern Arab publics to receive COVID-19 vaccines and investigated the factors behind any reluctance to receive them.MethodsA self-administered questionnaire was distributed through social media applications in four Arab countries (Jordan, Saudi Arabia, Lebanon, and Iraq). Participants’ demographics, medical history, their experience with COVID-19, and their willingness to receive the available vaccines were obtained and analyzed.ResultsA total of 2,925 completed forms were included. Only 25% of the participants were willing to receive a vaccine while 33% were hesitant. Iraqis were the most willing to receive it while Jordanians were the least (35% and 17% of each country, respectively). Interestingly, 60% of the acceptors were ready to pay for the vaccine if not covered by governments. It was also found that American vaccines were preffered by 50% of the acceptors. However, 30% of acceptors were unsure of which vaccine is the best and 11% stated that any vaccine is good. Social media were the major source of information about COVID-19 and its vaccines. Finally, predictors of acceptance of the vaccines included living in Saudi Arabia and Iraq, being unmarried, having monthly income > $1,000, holding a medical degree, having high fear from COVID-19, feeling of being at risk of getting infected with COVID-19, and previous reception of influenza vaccine, whereas predictors of refusal included female sex and previous infection with COVID-19.ConclusionMiddle Eastern Arabs are less likely to accept receiving the COVID-19 vaccines compared with non-Arabs. Health authorities in these countries are advised to intensify their awareness-raising activities about the vaccines while ensuring fair distribution of them.     

新型冠状病毒肺炎疫苗的临床试验研究进展

新型冠状病毒肺炎（COVID-19）大流行推动了COVID-19疫苗的研发速度。目前,已有99个COVID-19疫苗处于临床评价阶段,其中22个已进入临床III或IV期,许多疫苗已获紧急使用授权。本文对COVID-19疫苗的临床试验开展情况进行综述,旨在加深人们对COVID-19疫苗有效性和安全性的认识。     

法匹拉韦治疗新冠肺炎临床研究进展

新型冠状病毒肺炎(COVID-19)疫情在全球大流行,临床上迫切需要特异性抗病毒治疗药物。对已批准上市或正在临床开发的药物开展重定位研究是针对突发疫情快速寻找潜在治疗药物最为快速和高效的策略。法匹拉韦是一种广谱抗RNA病毒药物,在日本和中国已批准上市用于治疗流感,其作为抗新型冠状病毒感染的潜在药物,全球多个国家正在开展相关临床试验,初步的结果令人鼓舞。本文主要综述在中国、日本、俄罗斯和印度等国家开展的法匹拉韦单用或联合其他药物治疗COVID-19的临床试验,考察用药剂量、试验设计、药物有效性和安全性等。研究结果显示,法匹拉韦在针对COVID-19轻症和中症患者的治疗中,能够有效提高患者病毒RNA清除率或改善临床恢复率,且表现出良好的安全性。本文对法匹拉韦治疗COVID-19临床研究进展进行总结,为其在抗COVID-19治疗中的应用提供参考。     

新型冠状病毒肺炎临床治疗药物最新研究进展

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)正在世界范围内流行.作为冠状病毒,新型冠状病毒(SARS-CoV-2)和严重急性呼吸综合征冠状病毒(SARS-CoV)都通过人血管紧张素转化酶2(ACE2)受体侵入宿主细胞.面对疫情异常严峻的现状,目前尚缺乏疫苗和尚无特异性针对该病毒...     

雾化吸入药物疗法在COVI D-19治疗中的应用及药学监护

新型冠状病毒肺炎(COVID-19)疫情在全世界蔓延,针对COVID-19的临床诊治与药物治疗研究成为热点。目前,尚没有针对COVID-19的特效药物或疫苗,而多项相关的药物临床试验迅速开展,也引起广泛的关注。截至2020年3月18日,共有8项雾化吸入疗法治疗COVID-19的临床试验在国家临床试验中心注册,涉及7种药物。本文介绍了这7种药物的应用研究进展和雾化吸入药学监护,以加强药品使用的风险管理,减少药品使用的不良事件。     

Application of microfluidic technologies on COVID-19 diagnosis and drug discovery

The ongoing coronavirus disease 2019 (COVID-19) pandemic has boosted the development of antiviral research. Microfluidic technologies offer powerful platforms for diagnosis and drug discovery for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis and drug discovery. In this review, we introduce the structure of SARS-CoV-2 and the basic knowledge of microfluidic design. We discuss the application of microfluidic devices in SARS-CoV-2 diagnosis based on detecting viral nucleic acid, antibodies, and antigens. We highlight the contribution of lab-on-a-chip to manufacturing point-of-care equipment of accurate, sensitive, low-cost, and user-friendly virus-detection devices. We then investigate the efforts in organ-on-a-chip and lipid nanoparticles (LNPs) synthesizing chips in antiviral drug screening and mRNA vaccine preparation. Microfluidic technologies contribute to the ongoing SARS-CoV-2 research efforts and provide tools for future viral outbreaks.     

mRNA疫苗作用机制的研究进展

信使RNA（messenger RNA,mRNA）疫苗属于第三代疫苗,即核酸疫苗,具有细胞内表达速度快、有效性和安全性高、反应速度快、易规模化扩大和极具成本效益比等特点,在近30年中取得了突飞猛进的发展,越来越多的证据表明可以用合理的方法来提高这类现代疫苗的有效性和安全性。2020年暴发的由新型冠状病毒引起的新型冠状病毒肺炎大流行给全世界带来了巨大的灾难,导致了过亿例感染和数百万例死亡,疫苗被认为是阻断传播和控制疾病的唯一希望。在所有的疫苗种类中,mRNA疫苗极快的研发速度和有效性引起了广泛的关注。此综述就mRNA疫苗的体内摄取和抗原表达、固有免疫的作用、适应性免疫的激活、mRNA疫苗递送系统以及注射途径的效应等角度进行阐述,以期为mRNA疫苗的设计提供有价值的参考。     

A comparison between SARS-CoV-1 and SARS-CoV2: an update on current COVID-19 vaccines

Since the outbreak of the novel coronavirus disease 2019 (COVID-19) in Wuhan, China, many health care systems have been heavily engaged in treating and preventing the disease, and the year 2020 may be called as “historic COVID-19 vaccine breakthrough”. Due to the COVID-19 pandemic, many companies have initiated investigations on developing an efficient and safe vaccine against the virus. From Moderna and Pfizer in the United States to PastocoVac in Pasteur Institute of Iran and the University of Oxford in the United Kingdom, different candidates have been introduced to the market. COVID-19 vaccine research has been facilitated based on genome and structural information, bioinformatics predictions, epitope mapping, and data obtained from the previous developments of severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1) and middle east respiratory syndrome coronavirus (MERS-CoV) vaccine candidates. SARS-CoV genome sequence is highly homologous to the one in COVID-19 and both viruses use the same receptor, angiotensin-converting enzyme 2 (ACE2). Moreover, the immune system responds to these viruses, partially in the same way. Considering the on-going COVID-19 pandemic and previous attempts to manufacture SARS-CoV vaccines, this paper is going to discuss clinical cases as well as vaccine challenges, including those related to infrastructures, transportation, possible adverse reactions, utilized delivery systems (e.g., nanotechnology and electroporation) and probable vaccine-induced mutations.Graphical abstract      

中和抗体在新型冠状病毒肺炎治疗中的重要意义:进展与展望

SARS-CoV-2感染是对全世界人类生命和健康的一大严重威胁,新型冠状病毒肺炎是由SARS-CoV-2感染引起的全球流行病.SARS-CoV-2病毒具有高度的传染性、诡异性和多变性.因此,新型冠状病毒肺炎的治疗是紧迫且有针对性的.然而,疫苗和目前使用的药物一般不具有上述特点.虽然新型冠状病毒肺炎的恢复期血浆在危重患者...