Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street, St Petersburg, Russia.
Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street, St Petersburg, Russia.
Virology. 2018 May;518:313-323. doi: 10.1016/j.virol.2018.03.013. Epub 2018 Mar 22.
The development of influenza vaccines that can provide broad protection against all drifted seasonal virus variants, zoonotic infections and emerging pandemic strains, has been a priority for two decades. Here we propose a strategy of inducing broadly-reactive anti-stalk antibody by sequential immunizations with live attenuated influenza vaccines (LAIVs) expressing chimeric HAs (cHAs). These vaccines are designed to contain identical hemagglutinin stalk domains from H1N1 virus but antigenically unrelated globular head domains from avian influenza virus subtypes H5, H8 and H9. Mouse experiments demonstrated enhanced cross-protection of cHA-containing LAIVs compared to the relevant vaccine viruses expressing natural HAs, and this enhanced protection was driven by stalk-HA-reactive IgG antibodies. The establishment of fully functional cross-protective immunity after two doses of cHA LAIV vaccination in naïve animals suggests that a similar effect might be expected after a single cHA LAIV dose in primed individuals, or after two to three doses in naïve children.
二十年来，开发能够针对所有漂移季节性病毒变体、人畜共患感染和新兴大流行株提供广泛保护的流感疫苗一直是重中之重。在这里，我们提出了一种通过用表达嵌合 HA（cHA）的减毒活流感疫苗（LAIV）进行序贯免疫来诱导广谱抗茎部抗体的策略。这些疫苗设计包含来自 H1N1 病毒的相同血凝素茎域，但具有来自禽流感病毒亚型 H5、H8 和 H9 的抗原上无关的球形头部域。小鼠实验表明，与表达天然 HA 的相关疫苗病毒相比，含有 cHA 的 LAIV 具有增强的交叉保护作用，这种增强的保护作用是由茎-血凝素反应性 IgG 抗体驱动的。在无经验动物中进行两剂 cHA LAIV 接种后建立完全功能性的交叉保护免疫提示，在预先免疫的个体中单次 cHA LAIV 剂量后，或在无经验的儿童中接种两到三剂后，可能会产生类似的效果。
