Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses.
Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses.
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DOI：
10.1016/j.ymthe.2017.03.035
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发表时间：
2017-06-07
期刊：
影响因子：
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通讯作者：
Ciaramella G
中科院分区：
文献类型：
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作者：
Bahl K;Senn JJ;Yuzhakov O;Bulychev A;Brito LA;Hassett KJ;Laska ME;Smith M;Almarsson Ö;Thompson J;Ribeiro AM;Watson M;Zaks T;Ciaramella G
最近，世界卫生组织在中国确认了120例新的人感染H7N9禽流感病例，导致37人死亡，凸显了对潜在大流行的担忧以及对有效，安全和高速疫苗生产平台的需求。基于mRNA的疫苗的生产速度和规模使其非常适合阻止潜在的大流行威胁。在这里，我们表明，脂质纳米颗粒（LNP）配制的，修饰的mRNA疫苗，编码H10 N8（A/江西-东湖/346/2013）或H7 N9（A/安徽/1/2013）的血凝素（HA）蛋白，在小鼠，雪貂和非人灵长类动物中产生快速和强大的免疫应答，如血凝抑制（HAI）和微量中和（MN）测定所测量的。单剂量的H7N9 mRNA保护小鼠免受致命攻击，并降低雪貂的肺部病毒滴度。首次在人体内进行的、剂量递增的、1期H10 N8研究的中期结果显示，血清转化率非常高，表明在人体内具有强大的预防性免疫力。不良事件（AE）为轻度或中度，仅有少数重度事件，无严重事件。这些数据表明，LNP配制的修饰的mRNA疫苗可以诱导具有可接受耐受性特征的保护性免疫原性。潜在的大流行性流感以及对有效、安全和高速疫苗生产平台的需求已在科学界得到广泛讨论。Bahl等人报告了从具有可接受的安全性特征的修饰的mRNA疫苗获得的针对H10 N8和H7N9病毒的快速和稳健的免疫应答。
Recently, the World Health Organization confirmed 120 new human cases of avian H7N9 influenza in China resulting in 37 deaths, highlighting the concern for a potential pandemic and the need for an effective, safe, and high-speed vaccine production platform. Production speed and scale of mRNA-based vaccines make them ideally suited to impede potential pandemic threats. Here we show that lipid nanoparticle (LNP)-formulated, modified mRNA vaccines, encoding hemagglutinin (HA) proteins of H10N8 (A/Jiangxi-Donghu/346/2013) or H7N9 (A/Anhui/1/2013), generated rapid and robust immune responses in mice, ferrets, and nonhuman primates, as measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays. A single dose of H7N9 mRNA protected mice from a lethal challenge and reduced lung viral titers in ferrets. Interim results from a first-in-human, escalating-dose, phase 1 H10N8 study show very high seroconversion rates, demonstrating robust prophylactic immunity in humans. Adverse events (AEs) were mild or moderate with only a few severe and no serious events. These data show that LNP-formulated, modified mRNA vaccines can induce protective immunogenicity with acceptable tolerability profiles. Potential pandemic influenzas and the need for an effective, safe, and high-speed vaccine production platform have been widely discussed in the scientific community. Bahl et al. report the rapid and robust immune responses achieved against H10N8 and H7N9 viruses from modified mRNA vaccines with an acceptable safety profile.