Broadened immunity and protective responses with emulsion-adjuvanted H5 COBRA-VLP vaccines
Broadened immunity and protective responses with emulsion-adjuvanted H5 COBRA-VLP vaccines
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DOI：
10.1016/j.vaccine.2017.07.107
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发表时间：
2017-09-12
期刊：
影响因子：
5.5
通讯作者：
Ross, Ted M.
中科院分区：
文献类型：
--
作者：
Allen, James D.;Owino, Simon;Ross, Ted M.
开发大流行前的保护性甲型流感疫苗存在许多挑战，包括预测目标流感毒株和为免疫学上未接触过的人群设计疫苗。疫苗的制造和供应还需要采取措施，通过剂量节约方法增加对最大数量人群的覆盖，同时不损害疫苗的效力。此前，我们的小组描述了一种针对 H5N1 流感的新型血凝素 (HA)，其源自一种称为计算优化广泛反应性抗原 (COBRA) 的方法。本报告描述了一种将基于 COBRA 的 HA 疫苗与水包油乳剂相结合的策略，从而产生节省剂量、扩大免疫范围和针对多种 H5N1 分离株的保护性反应。在这里，我们证明基于乳液的佐剂增强了野生型 H5HA (H5N1 WT) 和 H5N1 COBRA HA VLP 疫苗的抗体反应的程度和广度。 H5N1 COBRA HA VLP 与乳剂佐剂相结合，引发针对更多 H5N1 病毒的 HAI 特异性抗体，从而与同源匹配疫苗一样有效地抵御攻击。 (C) 2017 Elsevier Ltd. 保留所有权利。
A number of challenges for developing a protective pre-pandemic influenza A vaccine exists including predicting the target influenza strain and designing the vaccine for an immunologically naive population. Manufacturing and supply of the vaccine would also require implementing ways to increase coverage for the largest number of people through dose-sparing methods, while not compromising the potency of the vaccine. Previously, our group described a novel hemagglutinin (HA) for H5N1 influenza derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This report describes a strategy combining a COBRA-based HA vaccine with an oil-in-water emulsion, resulting in a dose sparing, immunologically broadened, and protective response against multiple H5N1 isolates. Here, we show that an emulsion-based adjuvant enhances the magnitude and breadth of antibody responses with both a wild-type H5HA (H5N1 WT) and the H5N1 COBRA HA VLP vaccines. The H5N1 COBRA HA VLP, combined with an emulsion adjuvant, elicited HAI specific antibodies against a larger panel of H5N1 viruses that resulted in protection against challenge as efficiently as the homologous, matched vaccine. (C) 2017 Elsevier Ltd. All rights reserved.