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首页> 外文会议>Conference on vaccine technology VI >A PRE-FUSION, TRIMERIC SUBUNIT INFLUENZA HA-BASED VACCINE ELICITS CROSS-PROTECTION BETWEEN HIGHLY DIVERGENT INFLUENZA A VIRUSES
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A PRE-FUSION, TRIMERIC SUBUNIT INFLUENZA HA-BASED VACCINE ELICITS CROSS-PROTECTION BETWEEN HIGHLY DIVERGENT INFLUENZA A VIRUSES

机译：预融合，三聚亚基流感型HA基疫苗引发了高度发育的流感病毒之间的交叉保护

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Despite our best efforts to vaccinate against influenza viruses they remain a major cause of morbidity and mortality worldwide, resulting in 3-5 million severe infections and more than 250,000 deaths annually. Constant antigenic changes in circulating viruses means current vaccines must be updated and re-administered annually. This approach is time-consuming and expensive, and is often hindered by mismatches between circulating and vaccine strains. Strain mismatch can contribute to insufficient vaccine efficacy, which has ranged from just 10-60% over the last decade. Furthermore, recent sporadic zoonotic outbreaks of novel highly pathogenic viruses from avian species, to which current vaccines provide no immunity, have been observed, with fatality rates around 40%. This raises serious concerns of a global pandemic with the potential to spread rapidly before a vaccine can be manufactured. Novel approaches to influenza vaccination are clearly needed in order to overcome these limitations with "universal" flu vaccines being the holy grail. We have stabilized recombinant influenza haemagglutinin (rHA) in its native, pre-fusion conformation by the addition of a novel "clamp" stabilization motif to enhance subunit vaccine potency and breadth of protection. Immunisation of mice with clamp-stabilized prefusion rHA elicited a potent neutralizing antibody response (~4-fold improvement over current vaccines). Most importantly, antibodies elicited upon immunisation with clamp-stabilised prefusion rHA showed an 80-fold increase in cross-reactivity to rHA derived from a divergent, highly pathogenic avian virus (H5N1) when compared to the current influenza vaccines. We have also shown that vaccination with clamp-stabilisted rHA based on the H3 subtype (group 2) is capable of providing cross-protection to a challenge with a highly-divergent group 1 virus (H1N1). Ultimately, this approach could represent a potential universal influenza vaccine, providing enhanced cross-protection against both group 1 and 2 seasonal influenza virus strains while simultaneously providing an increased cross-reactive humoral immune response to potential zoonotic pandemic strains.
机译：尽管我们促进血型流感病毒的最佳努力，但它们仍然是全世界发病率和死亡率的主要原因，每年患3-50万严重的感染和超过250,000人死亡。循环病毒的恒定抗原变化意味着必须更新电流疫苗并每年重新施用。这种方法是耗时和昂贵的，并且通常在循环和疫苗菌株之间的不匹配受到不匹配。菌株不匹配可以有助于疫苗疗效不足，在过去十年中只有10-60％。此外，已经观察到来自禽类的新型高度致病病毒，目前疫苗不提供免疫的新型致症状病毒的峰值爆发，死亡率约为40％。这提高了全球大流行的严重关切，在可以制造疫苗之前迅速传播。清楚地需要新的流感疫苗接种方法，以克服这些限制与“普通”流感疫苗是圣杯。通过添加一种新的“夹钳”稳定基序，在其天然预熔融构象中稳定重组流感血凝素（RHA），以增强亚基疫苗效力和保护宽度。用夹紧稳定的排尿液体的小鼠的免疫引发了有效的中和抗体反应（对电流疫苗的〜4倍）。最重要的是，与钳位稳定的排尿液免疫引起的抗体显示出与当前流感疫苗相比，在发散的高致病性禽病毒（H5N1）中的交叉反应性增加了80倍的交叉反应性。我们还表明，基于H3亚型（第2组）的钳位稳定的RHA接种能够为具有高度发散组1病毒（H1N1）的攻击提供交叉保护。最终，这种方法可以代表潜在的通用流感疫苗，为第1组和2族季节性流感病毒株提供增强的交叉保护，同时为潜在的人畜共患病毒抑菌增加了增加的交叉反应性体液免疫应答。

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