Improving influenza vaccine virus selection: report of a WHO informal consultation held at WHO headquarters, Geneva, Switzerland, 14-16 June 2010.
Improving influenza vaccine virus selection: report of a WHO informal consultation held at WHO headquarters, Geneva, Switzerland, 14-16 June 2010.
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DOI：
10.1111/j.1750-2659.2011.00277.x
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发表时间：
2012-03
影响因子：
4.4
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
WHO Writing Group;Ampofo WK;Baylor N;Cobey S;Cox NJ;Daves S;Edwards S;Ferguson N;Grohmann G;Hay A;Katz J;Kullabutr K;Lambert L;Levandowski R;Mishra AC;Monto A;Siqueira M;Tashiro M;Waddell AL;Wairagkar N;Wood J;Zambon M;Zhang W
近60年来，世卫组织全球流感监测和反应系统（GISRS）一直是监测流感病毒演变和传播以及建议用于人流感疫苗的毒株的关键角色。GISRS还努力不断监测和评估潜在大流行性病毒构成的风险，并指导适当的公共卫生应对措施。在通过《国际卫生条例（2005）》之后，全球信息系统信息系统的作用得到扩大和加强，认识到H5N1禽流感造成的持续威胁以及2009年H1N1流感大流行的后果，为严格审查流感疫苗病毒的选择过程提供了一个时机。除了确定可能改进的领域外，这种审查还将有助于促进更广泛的流感和政策制定界对流感疫苗病毒选择的复杂性有更深的认识。选择过程是高度协调的，包括国家流感中心（NICs）持续全年整合病毒学数据和流行病学信息，世卫组织合作中心（whooccs）对病毒进行全面的抗原和遗传表征，作为选择合适候选疫苗病毒的一部分，以及世卫组织基本监管实验室（ERLs）为疫苗标准化准备合适的重组物和相应试剂。近年来，分子诊断的进步和更广泛的基因序列数据的可用性有助于确保疫苗的最佳有效性。然而，仍然存在一些具有挑战性的制约因素，包括所使用的检测方法存在差异，非抗原变化可能导致并发症，合适的疫苗病毒供应有限，以及由于生产限制，需要在流感季节高峰前最多一年提出建议。人们日益认识到，人类和动物流感网络之间的有效合作与协调是改善动物和人类病毒数据整合、识别感染人类的异常甲型流感病毒、评估大流行风险和选择大流行疫苗候选病毒的基本要求。培训讲习班、评估和捐赠使训练有素的实验室人员和设备大量增加，从而扩大了地理监测范围和国家卫生和其他实验室的能力。这导致向世卫组织报告的关于流感传播、强度和影响的信息量大大增加。此外，世卫组织运输基金项目等举措促进了及时分享临床标本和病毒分离物，并有助于更全面地了解不同病毒的全球分布和时间循环。重要的是要维持和扩大在这些领域和其他领域取得的成果。尽管在可预见的未来，血凝抑制（HAI）检测可能仍然是病毒抗原表征的首选检测方法，但其他检测方法——例如基于先进的重组DNA和蛋白质技术的检测方法——可能更适合自动化。其他技术，如微滴神经氨酸酶抑制试验，也可能对疫苗病毒选择和疫苗开发具有重要意义。微量中和试验是病毒抗原鉴定中HAI试验的重要补充。这种检测方法在使用和潜在自动化方面的改进应促进大规模血清学研究，而其他先进技术，如表位定位，应允许更准确地评估保护性免疫反应的质量，并有助于制定额外的免疫测量标准。通过标准化的血清流行病学调查来评估流感对人群的影响，有助于建立具有良好特征的年龄分层代表性血清库，作为国家、地区和全球资源，同时为疫苗接种的具体益处提供直接证据。高通量基因测序技术的进步，加上先进的生物信息学工具，以及更多的X射线晶体学数据，将加速对病毒进化背后的遗传和表型变化的理解，更具体地说，有助于预测氨基酸变化对病毒抗原性的影响。越来越多地使用复杂的数学建模技术来深入了解流感病毒的演变和流行病学。然而，它们在预测未来抗原和遗传变化的时间和性质方面的价值目前可能有限。应用更简单的非机械统计算法，例如已经用作抗原性制图基础的算法，以及系统发育建模，更可能有助于促进疫苗病毒的选择，并有助于评估禽流感和其他动物流感病毒的大流行潜力。采用替代疫苗技术，如减毒活疫苗、四价疫苗或非HA疫苗，对疫苗病毒选择以及疫苗监管和生产过程具有重大意义。GISRS与疫苗制造商之间最近的合作，增加了用于疫苗生产的蛋分离物和高生长重组物的可用性，开发了合格的细胞培养物，并研究了疫苗效力测试的替代方法。世卫组织将继续支持这些和其他努力，以提高全球流感疫苗供应的可靠性和及时性。世卫组织地理信息系统及其合作伙伴正在不断努力确定改进措施，利用新技术，加强和维持合作。世卫组织将继续发挥协调全球专门知识的中心作用，以满足公众对流感疫苗日益增长的卫生需求，并将支持改进疫苗病毒选择过程的努力，包括通过召开定期国际磋商。
For almost 60 years, the WHO Global Influenza Surveillance and Response System (GISRS) has been the key player in monitoring the evolution and spread of influenza viruses and recommending the strains to be used in human influenza vaccines. The GISRS has also worked to continually monitor and assess the risk posed by potential pandemic viruses and to guide appropriate public health responses. The expanded and enhanced role of the GISRS following the adoption of the International Health Regulations (2005), recognition of the continuing threat posed by avian H5N1 and the aftermath of the 2009 H1N1 pandemic provide an opportune time to critically review the process by which influenza vaccine viruses are selected. In addition to identifying potential areas for improvement, such a review will also help to promote greater appreciation by the wider influenza and policy‐making community of the complexity of influenza vaccine virus selection. The selection process is highly coordinated and involves continual year‐round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs). Ensuring the optimal effectiveness of vaccines has been assisted in recent years by advances in molecular diagnosis and the availability of more extensive genetic sequence data. However, there remain a number of challenging constraints including variations in the assays used, the possibility of complications resulting from non‐antigenic changes, the limited availability of suitable vaccine viruses and the requirement for recommendations to be made up to a year in advance of the peak of influenza season because of production constraints. Effective collaboration and coordination between human and animal influenza networks is increasingly recognized as an essential requirement for the improved integration of data on animal and human viruses, the identification of unusual influenza A viruses infecting human, the evaluation of pandemic risk and the selection of candidate viruses for pandemic vaccines. Training workshops, assessments and donations have led to significant increases in trained laboratory personnel and equipment with resulting expansion in both geographical surveillance coverage and in the capacities of NICs and other laboratories. This has resulted in a significant increase in the volume of information reported to WHO on the spread, intensity and impact of influenza. In addition, initiatives such as the WHO Shipment Fund Project have facilitated the timely sharing of clinical specimens and virus isolates and contributed to a more comprehensive understanding of the global distribution and temporal circulation of different viruses. It will be important to sustain and build upon the gains made in these and other areas. Although the haemagglutination inhibition (HAI) assay is likely to remain the assay of choice for the antigenic characterization of viruses in the foreseeable future, alternative assays – for example based upon advanced recombinant DNA and protein technologies – may be more adaptable to automation. Other technologies such as microtitre neuraminidase inhibition assays may also have significant implications for both vaccine virus selection and vaccine development. Microneutralization assays provide an important adjunct to the HAI assay in virus antigenic characterization. Improvements in the use and potential automation of such assays should facilitate large‐scale serological studies, while other advanced techniques such as epitope mapping should allow for a more accurate assessment of the quality of a protective immune response and aid the development of additional criteria for measuring immunity. Standardized seroepidemiological surveys to assess the impact of influenza in a population could help to establish well‐characterized banks of age‐stratified representative sera as a national, regional and global resource, while providing direct evidence of the specific benefits of vaccination. Advances in high‐throughput genetic sequencing coupled with advanced bioinformatics tools, together with more X‐ray crystallographic data, should accelerate understanding of the genetic and phenotypic changes that underlie virus evolution and more specifically help to predict the influence of amino acid changes on virus antigenicity. Complex mathematical modelling techniques are increasingly being used to gain insights into the evolution and epidemiology of influenza viruses. However, their value in predicting the timing and nature of future antigenic and genetic changes is likely to be limited at present. The application of simpler non‐mechanistic statistical algorithms, such as those already used as the basis of antigenic cartography, and phylogenetic modelling are more likely to be useful in facilitating vaccine virus selection and in aiding assessment of the pandemic potential of avian and other animal influenza viruses. The adoption of alternative vaccine technologies – such as live‐attenuated, quadrivalent or non‐HA‐based vaccines – has significant implications for vaccine virus selection, as well as for vaccine regulatory and manufacturing processes. Recent collaboration between the GISRS and vaccine manufacturers has resulted in the increased availability of egg isolates and high‐growth reassortants for vaccine production, the development of qualified cell cultures and the investigation of alternative methods of vaccine potency testing. WHO will continue to support these and other efforts to increase the reliability and timeliness of the global influenza vaccine supply. The WHO GISRS and its partners are continually working to identify improvements, harness new technologies and strengthen and sustain collaboration. WHO will continue in its central role of coordinating worldwide expertise to meet the increasing public health need for influenza vaccines and will support efforts to improve the vaccine virus selection process, including through the convening of periodic international consultations.