Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine:: a randomised controlled trial
Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine:: a randomised controlled trial
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DOI：
10.1016/s0140-6736(07)61297-5
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发表时间：
2007-08-18
期刊：
影响因子：
168.9
通讯作者：
Leroux-Roels, Geert
中科院分区：
文献类型：
--
作者：
Leroux-Roels, Isabel;Borkowski, Astrid;Leroux-Roels, Geert
由于全球流感疫苗生产能力有限，因此抗原保留被认为是大流行疫苗开发的关键。佐剂是一种重要的抗原保留策略。我们评估的安全性和免疫原性的重组H5 N1裂解病毒体疫苗配制与专有的佐剂系统，并调查它是否可以诱导交叉反应immunity.Methods两个剂量的灭活裂解A/越南/1194/2004 NIBRG-14（重组H5 N1基因工程的反向遗传学）疫苗的21天间隔八组50名志愿者年龄在18-60岁。我们研究了四种抗原剂量（3.8 μ g，7.5 μ g，15 μ g和30 μ g血凝素），有或没有佐剂。采集血样分析体液免疫反应。不良事件记录至研究第51天。安全性分析是整个接种队列的安全性分析，并根据方案进行免疫原性分析。该试验在ClinicalTrials.gov上注册，编号为NCT 00309634。未报告严重不良事件。与无佐剂疫苗相比，含佐剂疫苗诱导了更多的注射部位症状和全身症状，但大多数症状的强度为轻度至中度，且为一过性。在所有抗原剂量下，加佐剂制剂的免疫原性明显高于无佐剂制剂。在最低抗原剂量（3.8 μ g）下，针对重组同源疫苗株（A/Vietnam/1194/2004 NIBRG-14，进化枝1）的佐剂疫苗的免疫应答符合或超过所有美国食品药品监督管理局和欧盟许可标准。此外，48名接受3.8 μ g含佐剂疫苗的参与者中有37名（77%）血清转化，用于中和通过反向遗传学从漂移的H5 N1分离株（A/Indonesia/5/2005，进化枝2）衍生的菌株的抗体。此外，记录的交叉进化枝中和抗体应答意味着这种疫苗可以在大流行之前用于免疫接种。
Background Antigen sparing is regarded as crucial for pandemic vaccine development because worldwide influenza vaccine production capacity is limited. Adjuvantation is an important antigen-sparing strategy. We assessed the safety and immunogenicity of a recombinant H5N1 split-virion vaccine formulated with a proprietary adjuvant system and investigated whether it can induce cross-reactive immunity.Methods Two doses of an inactivated split A/Vietnam/1194/2004 NIBRG-14 (recombinant H5N1 engineered by reverse genetics) vaccine were administered 21 days apart to eight groups of 50 volunteers aged 18-60 years. We studied four antigen doses (3.8 mu g, 7.5 mu g, 15 mu g, and 30 mu g haemagglutinin) given with or without adjuvant. Blood samples were collected to analyse humoral immune response. Adverse events were recorded up through study day 51. Safety analyses were of the whole vaccinated cohort and immunogenicity analyses per protocol. This trial is registered with the ClinicalTrials.gov, number NCT00309634.Findings All eight vaccine formulations had a good safety profile. No serious adverse events were reported. The adjuvanted vaccines induced more injection-site symptoms and general symptoms than did the non-adjuvanted vaccines, but most were mild to moderate in intensity and transient in nature. The adjuvanted formulations were significantly more immunogenic than the non-adjuvanted formulations at all antigen doses. At the lowest antigenic dose (3.8 mu g), immune responses for the adjuvanted vaccine against the recombinant homologous vaccine strain (A/Vietnam/1194/2004 NIBRG-14, clade 1) met or exceeded all US Food and Drug Administration and European Union licensure criteria. Furthermore, 37 of 48 (77%) participants receiving 3.8 mu g of the adjuvanted vaccine seroconverted for neutralising antibodies against a strain derived by reverse genetics from a drifted H5N1 isolate (A/Indonesia/5/2005, clade 2).Interpretation Adjuvantation conferred significant antigen sparing that could increase the production capacity of pandemic influenza vaccine. Moreover, the cross-clade neutralising antibody responses recorded imply that such a vaccine could be deployed for immunisation before a pandemic.