Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
J Virol. 2014 Apr;88(8):3976-85. doi: 10.1128/JVI.03095-13. Epub 2014 Jan 22.
The emergence of avian H7N9 viruses in humans in China has renewed concerns about influenza pandemics emerging from Asia. Vaccines are still the best countermeasure against emerging influenza virus infections, but the process from the identification of vaccine seed strains to the distribution of the final product can take several months. In the case of the 2009 H1N1 pandemic, a vaccine was not available before the first pandemic wave hit and therefore came too late to reduce influenza morbidity. H7 vaccines based on divergent isolates of the Eurasian and North American lineages have been tested in clinical trials, and seed strains and reagents are already available and can potentially be used initially to curtail influenza-induced disease until a more appropriately matched H7N9 vaccine is ready. In a challenge experiment in the mouse model, we assessed the efficacy of both inactivated virus and recombinant hemagglutinin vaccines made from seed strains that are divergent from H7N9 from each of the two major H7 lineages. Furthermore, we analyzed the cross-reactive responses of sera from human subjects vaccinated with heterologous North American and Eurasian lineage H7 vaccines to H7N9. Vaccinations with inactivated virus and recombinant hemagglutinin protein preparations from both lineages raised hemagglutination-inhibiting antibodies against H7N9 viruses and protected mice from stringent viral challenges. Similar cross-reactivity was observed in sera of human subjects from a clinical trial with a divergent H7 vaccine. Existing H7 vaccine candidates based on divergent strains could be used as a first line of defense against an H7N9 pandemic. In addition, this also suggests that H7N9 vaccines that are currently under development might be stockpiled and used for divergent avian H7 strains that emerge in the future.
Sporadic human infections with H7N9 viruses started being reported in China in the early spring of 2013. Despite a significant drop in the number of infections during the summer months of 2013, an increased number of cases has already been reported for the 2013-2014 winter season. The high case fatality rate, the ability to bind to receptors in the human upper respiratory tract in combination with several family clusters, and the emergence of neuraminidase inhibitor-resistant variants that show no loss of pathogenicity and the ability to transmit in animal models have raised concerns about a potential pandemic and have spurred efforts to produce vaccine candidates. Here we show that antigen preparations from divergent H7 strains are able to induce protective immunity against H7N9 infection.
在中国，禽类 H7N9 病毒感染人类的情况再次引发了人们对亚洲流感大流行的担忧。疫苗仍然是对抗新发流感病毒感染的最佳对策，但从鉴定疫苗种子株到最终产品的分发过程可能需要数月时间。在 2009 年 H1N1 大流行期间，在第一波大流行浪潮来袭之前，还没有疫苗可用，因此为时已晚，无法降低流感发病率。基于欧亚和北美谱系的不同分离株的 H7 疫苗已在临床试验中进行了测试，种子株和试剂已经可用，并且可以在最初用于遏制流感引起的疾病，直到准备好更合适的 H7N9 疫苗。在小鼠模型的挑战实验中，我们评估了来自两个主要 H7 谱系的与 H7N9 不同的种子株制成的灭活病毒和重组血凝素疫苗的功效。此外，我们分析了接种异源北美和欧亚谱系 H7 疫苗的人类受试者血清的交叉反应性。来自临床试验的 H7 疫苗的异源血凝素蛋白制剂的接种会引起针对 H7N9 病毒的血凝抑制抗体，并保护小鼠免受严格的病毒挑战。在临床试验中，人类受试者的血清中也观察到了类似的交叉反应性。基于不同菌株的现有 H7 疫苗候选物可以作为对抗 H7N9 大流行的第一道防线。此外，这也表明，目前正在开发的 H7N9 疫苗可能会被储备起来，用于未来出现的不同禽类 H7 株。
2013 年初，中国开始报告零星的 H7N9 病毒感染人类病例。尽管 2013 年夏季感染人数有所下降，但在 2013-2014 年冬季，已报告的病例数有所增加。高病死率、能够与人类上呼吸道中的受体结合、以及出现神经氨酸酶抑制剂耐药变体，这些变体显示出对致病性和在动物模型中传播能力的无损失，这些都引发了人们对潜在大流行的担忧，并促使人们努力生产疫苗候选物。在这里，我们表明，来自不同 H7 株的抗原制剂能够诱导针对 H7N9 感染的保护性免疫。
