Villanueva-Cabezas Juan P, Coppo Mauricio J C, Durr Peter A, McVernon Jodie
Modelling and Simulation Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, Victoria, Australia; Australian Animal Health Laboratory, CSIRO, Geelong, Victoria, Australia.
Asia-Pacific Centre for Animal Health, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria, Australia.
Vaccine. 2017 Sep 5;35(37):4859-4869. doi: 10.1016/j.vaccine.2017.07.059. Epub 2017 Aug 2.
Indonesia has implemented multiple strategies to control Highly Pathogenic Avian Influenza H5N1 (HPAI/H5N1), including the licensure and use of multiple vaccine formulations. The continuous drift of Indonesian HPAI/H5N1 viruses and emergence of a new clade in 2012 that became dominant in 2016, demands the assessment of commercial vaccine formulations against Indonesian field viruses. Seven databases were explored to identify relevant literature reporting performance of commercial vaccines against Indonesian HPAI/H5N1 viruses. After methodological assessment, data were collated and analyzed to report immunogenicity and vaccine efficacy (VE) to prevent respiratory and cloacal viral shedding 2-day post challenge, and death at the end of the follow-up period. Meta-analyses were performed to assess VE consistency of alternative formulations and to explore sources of heterogeneity in VE. In total, 65 studies and 46 vaccine formulations from 13 articles were grouped per OIE's VE protocols (group 1) and variations of it (groups 2,3,4). We found that concurrence of vaccine-seed and challenge-viruses in a clade designation might be a better proxy of VE than current estimates based on vaccine-homologous HI antibody titers, particularly against current fourth order clade viruses (groups 1&2). Prime-boosting was efficacious across different chicken breeds (group 3), and early vaccination may increase the risk of death (group 4). One Indonesian vaccine was tested against the new dominant clade, conferring consistent protection in chickens but not in ducks. Meta-analyses revealed high inconsistency (I≥75%) and inefficacy of LPAI formulations against current field viruses, while potential sources of inconsistent VE were formulation of seed-homologous vaccines and the species vaccinated. We conclude that the VE of commercial vaccines in Indonesia changes as Indonesian HPAI/H5N1 evolve into new clades, which should warrant continuous matching between vaccine-seeds and emerging HPAI/H5N1. Furthermore, given the characteristics of the new Indonesian dominant HPAI/H5N1 clade, further studies to confirm VE across species are warranted.
印度尼西亚已实施多项策略来控制高致病性禽流感H5N1（HPAI/H5N1），包括批准和使用多种疫苗制剂。印度尼西亚HPAI/H5N1病毒的持续变异以及2012年出现的一个新分支在2016年成为优势分支，这就需要评估针对印度尼西亚野外病毒的商业疫苗制剂。研究人员检索了七个数据库，以识别报告商业疫苗针对印度尼西亚HPAI/H5N1病毒性能的相关文献。经过方法学评估后，对数据进行整理和分析，以报告免疫原性和疫苗效力（VE），从而预防攻毒后2天的呼吸道和泄殖腔病毒排出以及随访期结束时的死亡情况。进行荟萃分析以评估替代制剂的VE一致性，并探索VE异质性的来源。根据世界动物卫生组织（OIE）的VE方案（第1组）及其变体（第2、3、4组），总共对13篇文章中的65项研究和46种疫苗制剂进行了分组。我们发现，在分支分类中疫苗毒株和攻毒病毒的一致性可能比目前基于疫苗同源血凝抑制（HI）抗体滴度的估计值更能准确反映VE，特别是针对当前的第四分支病毒（第1和2组）。初免-加强免疫在不同鸡种中均有效（第3组），而早期接种疫苗可能会增加死亡风险（第4组）。一种印度尼西亚疫苗针对新的优势分支进行了测试，在鸡中提供了一致的保护，但在鸭中则不然。荟萃分析显示，低致病性禽流感（LPAI）制剂针对当前野外病毒的一致性较低（I≥75%）且效力不佳，而VE不一致的潜在来源是种子同源疫苗的配方和接种疫苗的物种。我们得出结论，随着印度尼西亚HPAI/H5N1演变成新的分支，印度尼西亚商业疫苗的VE也会发生变化，这就需要持续使疫苗毒株与新出现的HPAI/H5N1相匹配。此外，鉴于印度尼西亚新的优势HPAI/H5N1分支的特性，有必要进一步开展研究以确认不同物种间的VE情况。
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