新型冠状病毒肺炎疫苗有效性评价中的相关问题探讨

新型冠状病毒肺炎出现以来,席卷了全球各个国家和地区,安全且有效的新型冠状病毒肺炎疫苗是控制新型冠状病毒肺炎疫情最有效手段之一。新型冠状病毒肺炎疫苗的关键性临床研究通常采用安慰剂对照的保护效力试验,以观察疫苗是否可以有效降低疾病的发病率。本文即将对新冠疫苗保护效力临床试验中研究设计和研究终点的考量、统计学评价方法、主要估...     

加强新型冠状病毒疫苗效果评价, 助力科学精准防控

新型冠状病毒肺炎疫情在全球范围持续蔓延, 我国多地出现与输入病例关联的本土疫情。接种新型冠状病毒疫苗是预防新型冠状病毒发病、重症及死亡的最有效方法之一。针对我国研发和使用的疫苗种类, 利用不同的疫情暴发现场对各类变异株进行深入的真实世界研究, 并进一步推进针对变异株的疫苗研发和技术储备, 对科学精准防控尤为重要。本文探讨了新型冠状病毒病毒疫苗效果, 并对未来的疫苗效果评价研究、免疫策略研究及疫苗研发进行了展望, 为优化疫苗接种策略提供依据。     

新型冠状病毒疫苗研发策略综述

席卷全球的新型冠状病毒肺炎疫情给人类的生命健康安全带来巨大威胁,疫苗是防控疫情最为经济有效的手段。疫情暴发后,全球医药企业与科研机构快速启动了新型冠状病毒疫苗的研发,疫苗设计策略主要包括灭活疫苗、病毒载体疫苗、亚单位疫苗、减毒活疫苗和核酸疫苗等,经历1年的多方努力,目前已有多款疫苗相继公布Ⅲ期临床数据并获得紧急使用权限甚至被批准上市。本文将重点介绍新型冠状病毒疫苗免疫原靶标的选择,梳理当前不同类型疫苗的研究进展,并阐述新冠疫苗所面临的主要问题,以期为疫苗后续的改进提供有益借鉴。     

提高疫苗素养克服疫苗犹豫：疫苗素养研究进展与展望

 疫苗素养是应对新型冠状病毒肺炎(新冠肺炎)等疫苗可预防疾病的一项基本健康素养。本文拟对疫苗素养的界定、分类、测量和研究现状作综述,为提升居民疫苗素养,提高疫苗接种率,为有效建立免疫屏障提供理论和实践参考。     

实体器官移植受者新型冠状病毒疫苗接种临床研究进展

器官移植受者是新型冠状病毒肺炎的高风险人群,为降低该类患者的感染率及重症化率,疫苗接种是有效的防控方法.本文介绍实体器官移植受者感染新型冠状病毒的临床预后,综合分析该人群接受新冠疫苗后免疫应答相关机制及强化免疫的研究进展,并对该类患者的免疫策略提出建议.     

新型冠状病毒疫苗研发进展及接种意愿分析

新型冠状病毒肺炎（COVID-19）自2019年末爆发后迅速造成全球大流行,对公共卫生健康构成众大威胁。引发COVID-19的严重急性呼吸系统综合征冠状病毒-2（SARS-CoV-2）是高致病性病毒,各国采取多种防疫措施均未能从根本控制病毒传播,有效的疫苗对应控制疫情发生发展具有重要作用。各国通力合作,大力研发安全、有效的新型冠状病毒疫苗,本研究综述了新型冠状病毒疫苗研发的进展以及各国民众的疫苗接种意愿。     

新冠病毒疫苗序贯免疫策略研究进展

新型冠状病毒感染疫情（简称新冠疫情）的大流行,给全球生命安全和经济发展造成了严重影响。接种新型冠状病毒疫苗（简称新冠病毒疫苗）是预防新型冠状病毒（severe acute respiratory syndrome coronavirus 2,SARS-CoV-2）感染、降低其发病率和重症率的重要措施。目前全球共有6种不同技术路线的新冠病毒疫苗,即蛋白亚单位疫苗、核酸疫苗（mRNA疫苗和DNA疫苗）、病毒载体疫苗、灭活疫苗、病毒样颗粒疫苗、减毒活疫苗。序贯免疫策略是将不同技术路线的新冠病毒疫苗按照一定时间间隔、剂次完成接种,是解决疫苗短缺、应对病毒突变株、提高疫苗效力的有效策略,国内外很多学者开展了新冠病毒疫苗的序贯免疫策略研究。本文从新冠病毒灭活疫苗与mRNA疫苗、与腺病毒载体疫苗、与蛋白亚单位疫苗的序贯免疫策略及新冠病毒腺病毒载体疫苗与mRNA疫苗、与蛋白亚单位疫苗的序贯免疫策略5个方面对国内外新冠病毒疫苗序贯免疫策略的相关研究进行了概述,以期为新冠病毒疫苗的接种和免疫策略的制定提供参考依据。     

新型冠状病毒肺炎疫情防控面临的挑战

2019年12月湖北省武汉市报告的不明原因重症肺炎聚集性病例事件被确定为新型冠状病毒感染。WHO于2020年2月11日将该病命名为COVID-19。截至3月10日,新型冠状病毒肺炎已造成包括我国在内的114个国家和地区出现了11.8万病例。3月11日WHO评估认为,新型冠状病毒肺炎疫情已呈现大流行特征。当前新型冠状病毒肺炎防控工作面临巨大挑战,主要是由于病原溯源困难、传染源分布广泛、传播途径多样、易感人群免疫水平较低、传染性较强和疫苗研发尚需时日等因素的影响。     

肺炎球菌合并感染及肺炎球菌疫苗接种对新型冠状病毒肺炎临床预后的影响

由严重急性呼吸综合征冠状病毒 2 引起的新型冠状病毒肺炎已波及世界各国。肺炎球菌作为常见的社区获得性肺炎病原菌, 与新型冠状病毒肺炎具有相似的高危易感人群, 合并肺炎球菌感染是导致新型冠状病毒肺炎重症和死亡的关键危险因素。肺炎球菌疫苗接种对降低新型冠状病毒肺炎的发生率及死亡率具有积极的影响。我国肺炎球菌肺炎疫苗接种率较低, 对老年、存在慢性基础性疾病等高危人群接种肺炎球菌疫苗或是应对新型冠状病毒肺炎的有效措施之一。     

新型冠状病毒肺炎流行现状及应对策略进展

随着北半球秋冬季节来临,以呼吸道飞沫和密切接触传播为主要途径的新型冠状病毒肺炎(新冠肺炎,2019冠状病毒病)给各国防控带来了新的挑战。本文从新冠病毒变异、全球流行形势、群体免疫问题、无症状感染对我国疫情防控的影响、疫苗的进展和治疗等方面对新冠肺炎流行及应对现状进行综述,以期为新形势下我国疫情防控策略的规划和调整提供借鉴。     

International Collaboration to Ensure Equitable Access to Vaccines for COVID‐19: The ACT‐Accelerator and the COVAX Facility

Policy Points

• Equitable access to a COVID‐19 vaccine in all countries remains a key policy objective, but experience of previous pandemics suggests access will be limited in developing countries, despite the rapid development of three successful vaccine candidates.
• The COVAX Facility seeks to address this important issue, but the prevalence of vaccine nationalism threatens to limit the ability of the facility to meet both its funding targets and its ambitious goals for vaccine procurement.
• A failure to adequately address the underlying lack of infrastructure in developing countries threatens to further limit the success of the COVAX Facility.

ContextSignificant effort has been directed toward developing a COVID‐19 vaccine, which is viewed as the route out of the pandemic. Much of this effort has coalesced around COVAX, the multilateral initiative aimed at accelerating the development of COVID‐19 vaccines, and ensuring they are equitably available in low‐ and middle‐income countries (LMICs). This paper represents the first significant analysis of COVAX, and the extent to which it can be said to have successfully met these aims.MethodsThis paper draws on the publicly available policy documents made available by the COVAX initiatives, as well as position papers and public statements from governments around the world with respect to COVID‐19 vaccines and equitable access. We analyze the academic literature regarding access to vaccines during the H1N1 pandemic. Finally, we consider the WHO Global Allocation System, and its principles, which are intended to guide COVAX vaccine deployment.FindingsWe argue that the funding mechanism deployed by the COVAX Pillar appears to be effective at fostering at‐risk investments in research and development and the production of doses in advance of confirmation of clinical efficacy, but caution that this represents a win‐win situation for vaccine manufacturers, providing them with opportunity to benefit regardless of whether their vaccine candidate ever goes on to gain regulatory approval. We also argue that the success of the COVAX Facility with respect to equitable access to vaccine is likely to be limited, primarily as a result of the prevalence of vaccine nationalism, whereby countries adopt policies which heavily prioritize their own public health needs at the expense of others.ConclusionsCurrent efforts through COVAX have greatly accelerated the development of vaccines against COVID‐19, but these benefits are unlikely to flow to LMICs, largely due to the threat of vaccine nationalism.

A vaccine is viewed as the key to bringing about the end of the COVID‐19 pandemic. The sooner a vaccine is available, the sooner the world can begin to escape the acute phase of the pandemic, suppressing mortality and morbidity caused by infection and restoring a degree of normality to social life and the global economy. Not only is global equitable access to a COVID‐19 vaccine an important public health tool, but it is also necessary to ensure that all countries can discharge their human rights obligations. ¹ In an attempt to accelerate the availability of vaccines and other tools to combat COVID‐19, the World Health Organization (WHO) established the Access to COVID‐19 Tools (ACT) Accelerator, a global initiative designed to harbor international cooperation and knowledge regarding the pandemic. Specifically, the ACT‐Accelerator is focused on accelerating development in four areas, or pillars: diagnostics, therapeutics, vaccines (called COVAX), and health systems strengthening.Although efforts to develop a vaccine are starting to prove successful, with the development of successful candidates from Pfizer, Moderna, and AstraZenica/University of Oxford all receiving emergency regulatory approval in late 2020, key questions remain about which countries will have access to these vaccines, when they will get access, and in what quantities. During the 2009 H1N1 influenza pandemic, procurement of pandemic vaccines was dominated by developed countries, which used advance purchase agreements to reserve doses ahead of production. This severely limited the number of doses available in developing countries. ² In addition to accelerating research and development (R&D) through the ACT‐Accelerator, and in an attempt to ensure more equitable access to vaccines for COVID‐19, the Coalition for Epidemic Preparedness Innovations (CEPI); Gavi, the Vaccine Alliance; and the WHO formed the COVAX Facility in early 2020. The COVAX Facility is designed to address the issues encountered by developing countries during the 2009 H1N1 pandemic by using significant advance market commitments to secure access to vaccines on their behalf. It also encourages multilateral cooperation to increase access to vaccines in all participating countries.This paper argues that the funding mechanism deployed by the COVAX pillar appears to be effective at fostering at‐risk investments in R&D and the production of doses in advance of confirmation of clinical efficacy. Indeed, the development of two vaccine candidates funded by the ACT‐Accelerator is testament to this fact. However, this comes with a caution that the mechanism heavily favors pharmaceutical companies, for which up‐front investment from the COVAX pillar represents a win‐win situation and an opportunity to benefit regardless of whether their vaccine candidate ever goes on to gain regulatory approval. The paper then discusses the COVAX Facility, arguing that, like any multilateral purchasing system, securing a sufficient degree of interest and participation is essential to its success. It argues that the COVAX Facility has so far failed to do this, primarily as a result of the prevalence of vaccine nationalism, whereby countries adopt policies that heavily prioritize their own public health needs at the expense of others, and that its success is therefore likely to be limited. The paper concludes by arguing that the Global Allocation System, designed by the WHO, fails to address the issues experienced by the Vaccine Deployment Initiative during the 2009 H1N1 pandemic, specifically the delays in deploying vaccine in developing countries owing to a lack of preparedness and vaccine utilization infrastructure. It argues that, if these issues are not addressed, the COVAX Facility will fail to secure equitable access to vaccines in developing countries, despite the rapid development of successful vaccine candidates, because the allocation framework will be unable to operate as intended.     

Vaccines for a healthy future: 21st DCVMN Annual General Meeting 2020 report

The Developing Countries Vaccine Manufacturers' Network held its 21st Annual General Meeting virtually in November 2020 given the COVID-19 pandemic. Vaccine manufacturing experts, leaders from local and global public health organizations and multilateral organizations, through diverse presentations, questions and answers, focused on the pandemic and the response of vaccine manufacturers where many are engaged in research and development and production agreements. The pandemic is expanding rapidly which makes the global availability and equitable access to safe and effective COVID-19 vaccines critical. Strategies put in place include the establishment of the Access to COVID-19 Tools Accelerator (ACT-A) within which the COVAX facility aims to distribute 2 billion COVID-19 vaccine doses by the end of 2021, with procurement mechanisms already being established. At the same time, regulatory authorities have emergency use authorizations aimed at the rapid approval of safe and effective vaccines, with a push for harmonization in regulatory approaches being advocated. The Meeting was also apprised of other innovations being developed for vaccines including multi-array patches for easier vaccine application, increased heat stability for mitigating cold chain and storage challenges, the barcoding of primary packaging for enhancing vaccine traceability, and gathering data for decision-making. Over time, these innovations will facilitate the widespread availability and equitable access of vaccines including those addressing epidemics and pandemics. In addition, a number of manufacturers described technologies they have for accelerating vaccine manufacturing and supply globally.Overall, there was agreement that manufacturers from developing countries play a critical role in the global research, development and supply of vaccines for a healthy future, with increasing collaboration and partnering between them a growing strength.     

世界银行全球卫生安全合作策略及启示

以世界银行集团为首的国际开发性金融机构,作为全球治理的重要参与者之一,在维护全球卫生安全、提升本机构及合作国家应对大流行和突发公共卫生事件的能力、建立新型合作伙伴关系方面投入大量人、财、物力。本文通过系统梳理世界银行既往在卫生安全等卫生健康领域的战略规划、工作重点、筹资方式、全球伙伴关系等,以此次应对新冠疫情为例,深度剖析世界银行广泛参与并支持各国应对大流行的策略、进展、阶段性成效和挑战,对我国参与全球卫生治理,深化与国际金融开发机构开展卫生安全合作、创新合作模式提出建议。     

Estimating global changes in routine childhood vaccination coverage during the COVID-19 pandemic, 2020–2021

ObjectivesThe COVID-19 pandemic has disrupted the distribution of routine immunizations globally. Multi-country studies assessing a wide spectrum of vaccines and their coverage rates are needed to determine global performance in achieving vaccination goals.MethodsGlobal vaccine coverage data for 16 antigens were obtained from WHO/UNICEF Estimates of National Immunization Coverage. Tobit regression was performed for all country-antigen pairs for which data were continuously available between 2015–2020 or 2015–2021 to predict vaccine coverage in 2020/2021. Vaccines for which multi-dose data were available were assessed to determine whether vaccine coverage for subsequent doses were lower than that of first doses.ResultsVaccine coverage was significantly lower-than-predicted for 13/16 antigens in 2020 and all assessed antigens in 2021. Lower-than-predicted vaccine coverage was typically observed in South America, Africa, Eastern Europe, and Southeast Asia. There was a statistically significant coverage drop for subsequent doses of the diphtheria-tetanus-pertussis, pneumococcus, and rotavirus vaccines compared to first doses in 2020 and 2021.ConclusionThe COVID-19 pandemic exerted larger disruptions to routine vaccination services in 2021 than in 2020. Global efforts will be needed to recoup vaccine coverage losses sustained during the pandemic and broaden vaccine access in areas where coverage was previously inadequate.     

The Anticipated Future of Public Health Services Post COVID-19: Viewpoint

In March 2020, the World Health Organization declared COVID-19 as a global pandemic. The COVID-19 pandemic has affected various public health functions and essential services in different ways and magnitudes. Although all countries have witnessed the effect of COVID-19, the impact differed based on many factors including the integrity and resiliency of the countries’ health systems. This paper presents opinions and expectations of the authors about the anticipated changes in the future of public health at the global, regional, and national levels. The viewpoint is based on the current efforts and challenges that various stakeholders have carried out to control COVID-19 and the contribution from the literature on the future of public health. Numerous agencies and actors are involved in the fight against COVID-19 with variations in their effectiveness. The public health services showed weaknesses in most of the countries, in addition to the lack of adequate curative medicine settings. The pandemic highlighted the need for better governance and stronger and more resilient health systems and capacities. The COVID-19 experience has also emphasized the importance of coordination and collaboration among the countries and stakeholders. The COVID-19 pandemic might lead to a wide discussion to improve international and national approaches to prepare for and respond to similar events in terms of preparedness and response mechanisms and tools. Public health will not be the same as before COVID-19. New health priorities, approaches, and new agendas will be on the table of the global platforms and initiatives. More investment in research and technology to meet the demand for new vaccines and medicines, innovative methods like distance learning and working, more respect and remuneration to health professionals, and normalization of the public health and social measures that were induced during the COVID-19 pandemic are expected to be seen in future.     

Vaccines: New challenges,new paradigms,new opportunities: Report of the 22nd DCVMN Annual General Meeting

The Developing Countries Vaccine Manufacturers Network held its 22nd Annual General Meeting in October 2021. Vaccine manufacturing experts, leaders from global public health organizations and dignitaries from governments and multilateral organizations discussed the challenges and opportunities emerging from the COVID-19 pandemic. Over 350 delegates from 33 countries, representing over 70 organizations partook in the meetings deliberations.The development and scaled-up production of several safe and effective vaccines against COVID-19 resulted in over 12 billion doses being produced by the end of 2021. Unfortunately, this scientific achievement and outstanding industry effort has been overshadowed by the striking inequity in access to COVID-19 vaccines. High and upper middle-income countries have received 75% of the vaccines, while in Africa, less than 5% of the people are fully vaccinated. The inequitable access to vaccines is an issue of national health security, which has stressed the need to establish local vaccine manufacturing capacity in Africa. Key partnerships, initiatives and the deliberate strategies required to achieve sustainable manufacturing on the continent were discussed. The ability to acquire technology, access markets and financing mechanisms, and workforce development were reported as key enablers to achieving a healthy ecosystem.Innovative vaccine technologies, new regulatory approaches, and the importance of voluntary technology transfers in increasing the global supply capacity of both COVID-19 vaccines and traditional vaccines were highlighted. In reviewing the lessons learned from the pandemic, speakers shared a consensus that innovation and partnerships will be central to any solution proposed to mitigate the current pandemic and prepare for future ones.     

A cross-national study of multilevel determinants on public fully vaccination against COVID-19

The pandemic caused by SARS-CoV-2 (COVID-19) has impacted the world for close to three years and led to substantial costs to public well-being. To mitigate the pandemic's damage, the most effective approach lies in the vaccine. This study aims to investigate multilevel predictors of the public decision to become fully vaccinated against COVID-19. Data from a cross-national survey on representative samples are merged with country-level indicators. Multilevel logistic regression models are estimated on populations from 15 countries. Findings show that people who agree the government handles the pandemic well, believe the health officials would provide an effective vaccine, perceive the virus's danger, and are older are more likely to get fully vaccinated than their counterparts. Meanwhile, the national case rate and vaccination rate also affect one's decision to become fully vaccinated. Furthermore, there are significant cross-level interactions as people are more inclined to become fully vaccinated if they agree with the government's performance, perceive the virus's danger, and also reside in countries with higher case and vaccination rates. This study shows cross-national evidence regarding multilevel determinants of public vaccine uptake. Knowing the profiles among populations who have become fully vaccinated or not helps public health experts leverage factors and maximize vaccination.     

Global production capacity of seasonal and pandemic influenza vaccines in 2019

Vaccines will be an important element in mitigating the impact of an influenza pandemic. While research towards developing universal influenza vaccines is ongoing, the current strategy for vaccine supply in a pandemic relies on seasonal influenza vaccine production to be switched over to pandemic vaccines. Understanding how much vaccine could be produced, in which regions of the world and in what timeframe is critical to informing influenza pandemic preparedness. Through the Global Action Plan for Influenza Vaccines, 2006–2016, WHO promoted an increase in vaccine production capacity and monitors the landscape through periodically surveying influenza vaccine manufacturers. This study compares global capacity for production of influenza vaccines in 2019 with estimates from previous surveys; provides an overview of countries with established production facilities; presents vaccine production by type and manufacturing process; and discusses limitations to these estimates. Results of the current survey show that estimated annual seasonal influenza vaccine production capacity changed little since 2015 increasing from 1.47 billion to 1.48 billion doses with potential maximum annual influenza pandemic vaccine production capacity increasing from 6.37 billion to 8.31 billion doses. However, this figure should be interpreted with caution as it presents a best-case scenario with several assumptions which may impact supply. Further, pandemic vaccines would not be immediately available and could take four to six months for first supplies with several more months needed to reach maximum capacity. A moderate-case scenario is also presented of 4.15 billion doses of pandemic vaccine in 12 months. It is important to note that two doses of pandemic vaccine are likely to be required to elicit an adequate immune response. Continued efforts are needed to ensure the sustainability of this production and to conduct research for vaccines that are faster to produce and more broadly protective taking into account lessons learned from COVID-19 vaccine development.     

Unhealthy geopolitics: can the response to COVID-19 reform climate change policy?

The geopolitics of pandemics and climate change intersect. Both are complex and urgent problems that demand collective action in the light of their global and trans-boundary scope. In this article we use a geopolitical framework to examine some of the tensions and contradictions in global governance and cooperation that are revealed by the pandemic of coronavirus disease 2019 (COVID-19). We argue that the pandemic provides an early warning of the dangers inherent in weakened international cooperation. The world’s states, with their distinct national territories, are reacting individually rather than collectively to the COVID-19 pandemic. Many countries have introduced extraordinary measures that have closed, rather than opened up, international partnership and cooperation. Border closures, restrictions on social mixing, domestic purchase of public health supplies and subsidies for local industry and commerce may offer solutions at the national level but they do not address the global strategic issues. For the poorest countries of the world, pandemics join a list of other challenges that are exacerbated by pressures of scarce resources, population density and climate disruption. COVID-19’s disproportionate impact on those living with environmental stresses, such as poor air quality, should guide more holistic approaches to the geopolitical intersection of public health and climate change. By discussing unhealthy geopolitics, we highlight the urgent need for a coordinated global response to addressing challenges that cannot be approached unilaterally.