全球冠状病毒疫苗专利分析

冠状病毒是一类可感染人类和动物的RNA病毒,可引起严重急性呼吸综合征(SARS)和中东呼吸综合征(MERS)等严重疾病。新型冠状病毒是以前从未在人体中发现的冠状病毒新毒株,其人际传播迅速,引起了各国政府的高度重视并积极寻求疫苗防控对策。基于冠状病毒疫苗领域全景专利,在综合对比分析该领域的全部专利的发展趋势、主要国家和主要机构的专利产出的同时,重点揭示了其中的人用相关疫苗的发展与分布情况以及重点分析了人用疫苗产品的研发现状,以期为我国冠状病毒疫苗领域的科研工作者和管理决策者提供参考数据。     

全球冠状病毒疫苗专利分析

冠状病毒是一类可感染人类和动物的RNA病毒,可引起严重急性呼吸综合征(SARS)和中东呼吸综合征(MERS)等严重疾病。新型冠状病毒是以前从未在人体中发现的冠状病毒新毒株,其人际传播迅速,引起了各国政府的高度重视并积极寻求疫苗防控对策。基于冠状病毒疫苗领域全景专利,在综合对比分析该领域的全部专利的发展趋势、主要国家和主要机构的专利产出的同时,重点揭示了其中的人用相关疫苗的发展与分布情况以及重点分析了人用疫苗产品的研发现状,以期为我国冠状病毒疫苗领域的科研工作者和管理决策者提供参考数据。     

禽流感病毒新型疫苗的研究进展

疫苗免疫是禽流感防控的主要措施之一,随着生物技术的不断发展,基因工程亚单位疫苗、活载体疫苗、DNA疫苗等新型疫苗得以研究和开发,这为禽流感的防控提供了新的手段。新型疫苗除具有传统疫苗的保护效果外,在生物安全和普遍防控等方面也具有广泛的优势,是禽流感疫苗发展的新方向。     

A、B、C三型流感病毒病毒学、流行病学、临床特征和流感疫苗

２０世纪人类遭受了４次流感大流行,数千万人失去了生命,流感病毒分Ａ、Ｂ、Ｃ三型,对其病毒学、流行病学和临床特征,以及流感病毒传统疫苗－－灭活疫苗和新型疫苗－－核酸疫苗的研究进展作了论述。     

冷适应减毒B型流感病毒疫苗候选株的制备及鉴定

以冷适应、温度敏感、减毒的B/Ann Arbor/1/66流感病毒株作为重配病毒骨架,对其6个内部基因片段进行了全基因合成,同时人工引入9个氨基酸突变．构建了8个基因的拯救载体,经测序获得序列准确的拯救质粒,命名为：pAB121-PB1, pAB122-PB2, pAB123-PA, pAB124-HA, pAB125-NP, pAB126-NA, pAB127-M和pAB128-NS．在成功拯救冷适应A型流感病毒的基础上,利用反向遗传学技术成功获救了具有感染性的重配B型流感病毒株,命名为rMDV-B．该重配病毒株以B/Ann Arbor/1/66为病毒骨架,其中HA和NA来源于2006～2007年当年流行株B/Malaysia/2506/2004．rMDV-B在鸡胚尿囊液和MDCK细胞中的HA效价可达1∶64～1∶512．实验结果暗示：从单一供体病毒株可以产生有效的减毒活B型流感病毒疫苗候选株,能够为将来人用流感疫苗的设计提供可借鉴的模型．     

Development of a Mouse-Adapted Live Attenuated Influenza Virus That Permits In Vivo Analysis of Enhancements to the Safety of Live Attenuated Influenza Virus Vaccine

The live attenuated influenza virus vaccine (LAIV) is preferentially recommended for use in persons 2 through 49 years of age but has not been approved for children under 2 or asthmatics due to safety concerns. Therefore, increasing safety is desirable. Here we describe a murine LAIV with reduced pathogenicity that retains lethality at high doses and further demonstrate that we can enhance safety in vivo through mutations within NS1. This model may permit preliminary safety analysis of improved LAIVs.     

A Novel Influenza Virus Hemagglutinin-Respiratory Syncytial Virus (RSV) Fusion Protein Subunit Vaccine against Influenza and RSV

Influenza A virus and respiratory syncytial virus (RSV) cause substantial morbidity and mortality afflicting the ends of the age spectrum during the autumn through winter months in the United States. The benefit of vaccination against RSV and influenza using a subunit vaccine to enhance immunity and neutralizing antibody was investigated. Influenza virus hemagglutinin (HA) and RSV fusion (F) protein were tested as vaccine components alone and in combination to explore the adjuvant properties of RSV F protein on HA immunity. Mice vaccinated with HA and F exhibited robust immunity that, when challenged, had reduced viral burden for both influenza and RSV. These studies show an enhancing and cross-protective benefit of F protein for anti-HA immunity.     

一种用于流感病毒亚单位疫苗纯度分析的改进方法

目的：在SDS-PAGE方法的基础上建立一种改进方法,用于流感病毒亚单位疫苗中间体的杂质分析。方法：用糖苷酶F对不同亚型的疫苗中间体去糖基化处理后进行SDS-PAGE,与未经去糖基化处理的还原型SDS-PAGE结果进行比较。结果：去糖基化处理消除了血凝素的糖基化对电泳迁移率的影响,从而实现了血凝素亚基和杂质的电泳分离。结论：此方法应用于流感病毒亚单位疫苗中间体的杂质分析,较之常规的还原型SDS-PAGE方法具有更高的分辨力。     

A型流感病毒血凝素、神经氨酸酶DNA疫苗研究

用BALB/C小鼠为模型,检测A型流感病毒血凝素、神经氨酸酶、基质蛋白DNA疫苗抗流感能力。研究表明:血凝素、神经氨酸酶DNA疫苗能提供有效的抗流感保护;血凝素、神经氨酸酶和基质蛋白联合免疫动物提供最佳免疫保护。     

脂肪酶研发态势的全球专利分析

脂肪酶作为一种能够催化各种酯键断裂和形成的绿色环保生物催化剂,已被广泛应用于食品、饲料、洗涤剂、制药、精细化学以及生物修复等领域。基于智慧芽数据库（Pat Snap）对2020年10月前全球范围内各个国家及地区的脂肪酶相关专利进行统计,分析脂肪酶的技术分布、发展状况和未来趋势,并对比分析我国的脂肪酶研发现状,以期为脂肪酶技术及产业发展方向提供参考依据。     

A型流感病毒M2蛋白疫苗的研究进展

目前用于免疫人群的流感疫苗多为三价灭活疫苗,包含A型流感病毒H1N1亚型、H3N2亚型和B型流感病毒。多年来的实践表明,三价灭活疫苗是有一定保护效果的。但是,由于流感病毒血凝素(HA)和神经氨酸酶(NA)经常发生抗原转变和抗原漂移,使其抗原性表现出很大的变异,所以根据流感疫情监测预测的疫苗株也很难产生最理想的保护效果。但流感病毒基质蛋白M2的膜外区氨基酸序列高度保守,有可能发展成为具有交叉保护能力的流感疫苗的候选抗原。该文就A型流感病毒基质蛋白M2疫苗的研究作一综述。1 A型流感病毒基质蛋白M2结构及功能流感病毒基因组RN…     

全球转基因玉米专利信息分析与技术展望 *

转基因玉米是当前全球第二大转基因作物,在保障人类能源、饲料、工业等方面发挥着重要作用。基于智慧芽数据库(PatSnap)对欧盟、美国及中国等国家或地区收录的1985~2018年全球转基因玉米技术领域专利文献进行统计分析,得出全球转基因玉米专利技术发展的总体趋势、技术分布与格局及研发热点,并对比分析了国内外主要研发单位转基因玉米研发的竞争力,对未来转基因玉米的产业发展提出了展望。     

全球转基因大豆专利信息分析与技术展望

转基因大豆作为目前转基因作物推广种植面积最广的作物,在保障人类油料与饲料供给上发挥着重要作用。基于智慧芽数据库(PatSnap)对欧盟、美国及中国等国家地区1985~2016年收录的全球转基因大豆技术领域专利文献进行统计分析,得出全球转基因大豆专利信息的总体发展趋势、研发热点及技术分布与格局,并对比分析了我国转基因大豆研发的竞争力,对未来转基因大豆的产业发展提出了展望。     

Global Myeloma Research Clusters,Output, and Citations: A Bibliometric Mapping and Clustering Analysis

Background

International collaborative research is a mechanism for improving the development of disease-specific therapies and for improving health at the population level. However, limited data are available to assess the trends in research output related to orphan diseases.

Methods and Findings

We used bibliometric mapping and clustering methods to illustrate the level of fragmentation in myeloma research and the development of collaborative efforts. Publication data from Thomson Reuters Web of Science were retrieved for 2005–2009 and followed until 2013. We created a database of multiple myeloma publications, and we analysed impact and co-authorship density to identify scientific collaborations, developments, and international key players over time. The global annual publication volume for studies on multiple myeloma increased from 1,144 in 2005 to 1,628 in 2009, which represents a 43% increase. This increase is high compared to the 24% and 14% increases observed for lymphoma and leukaemia. The major proportion (>90% of publications) was from the US and EU over the study period. The output and impact in terms of citations, identified several successful groups with a large number of intra-cluster collaborations in the US and EU. The US-based myeloma clusters clearly stand out as the most productive and highly cited, and the European Myeloma Network members exhibited a doubling of collaborative publications from 2005 to 2009, still increasing up to 2013.

Conclusion and Perspective

Multiple myeloma research output has increased substantially in the past decade. The fragmented European myeloma research activities based on national or regional groups are progressing, but they require a broad range of targeted research investments to improve multiple myeloma health care.     

A DNA Vaccine against Yellow Fever Virus: Development and Evaluation

Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies.     

Protective Efficacy and Immunogenicity of a Combinatory DNA Vaccine against Influenza A Virus and the Respiratory Syncytial Virus

The Respiratory Syncytial Virus (RSV) and Influenza A Virus (IAV) are both two major causative agents of severe respiratory tract infections in humans leading to hospitalization and thousands of deaths each year. In this study, we evaluated the immunogenicity and efficacy of a combinatory DNA vaccine in comparison to the single component vaccines against both diseases in a mouse model. Intramuscular electroporation with plasmids expressing the hemagglutinin (HA) of IAV and the F protein of RSV induced strong humoral immune responses regardless if they were delivered in combination or alone. In consequence, high neutralizing antibody titers were detected, which conferred protection against a lethal challenge with IAV. Furthermore, the viral load in the lungs after a RSV infection could be dramatically reduced in vaccinated mice. Concurrently, substantial amounts of antigen-specific, polyfunctional CD8⁺ T-cells were measured after vaccination. Interestingly, the cellular response to the hemagglutinin was significantly reduced in the presence of the RSV-F encoding plasmid, but not vice versa. Although these results indicate a suppressive effect of the RSV-F protein, the protective efficacy of the combinatory vaccine was comparable to the efficacy of both single-component vaccines. In conclusion, the novel combinatory vaccine against RSV and IAV may have great potential to reduce the rate of severe respiratory tract infections in humans without increasing the number of necessary vaccinations.