Abstract：
H7N3 and H7N7 are highly pathogenic avian influenza (HPAI) viruses and have posed a great threat not only for the poultry industry but for the human health as well. H7N9, a low pathogenic avian influenza (LPAI) virus, is also highly pathogenic to humans, and there is a great concern that these H7 subtypes would acquire the ability to spread efficiently between humans, thereby becoming a pandemic threat. A vaccine candidate covering all the three subtypes must, therefore, be an integral part of any pandemic preparedness plan. To address this need, we constructed a consensus hemagglutinin (HA) sequence of H7N3, H7N7, and H7N9 based on the data available in the NCBI in early 2012-2015. This artificial sequence was then optimized for protein expression before being transformed into an attenuated auxotrophic mutant of Salmonella Typhimurium, JOL1863 strain. Immunizing chickens with JOL1863, delivered intramuscularly, nasally or orally, elicited efficient humoral and cell mediated immune responses, independently of the route of vaccination. Our results also showed that JOL1863 deliver efficient maturation signals to chicken monocyte derived dendritic cells (MoDCs) which were characterized by upregulation of costimulatory molecules and higher cytokine induction. Moreover, immunization with JOL1863 in chickens conferred a significant protection against the heterologous LPAI H7N1 virus challenge as indicated by reduced viral sheddings in the cloacal swabs. We conclude that this vaccine, based on a consensus HA, could induce broader spectrum of protection against divergent H7 influenza viruses and thus warrants further study.
摘要：
H7N3和H7N7是高致病性禽流感（HPAI）病毒，不仅对家禽业而且对人类健康构成了巨大威胁。H7N9，一种低致病性禽流感（LPAI）病毒，对人类也有很高的致病性，人们非常担心这些H7亚型会获得在人类之间有效传播的能力，从而成为大流行威胁。涵盖所有三种亚型的候选疫苗必须，因此,是任何大流行防备计划的组成部分。为了满足这一需求，我们根据2012-2015年初NCBI提供的数据构建了H7N3,H7N7和H7N9的共有血凝素(HA)序列.然后将该人工序列优化用于蛋白质表达，然后转化为鼠伤寒沙门氏菌的减毒营养缺陷型突变体，JOL1863菌株。用JOL1863对鸡进行免疫，肌肉注射，经鼻或经口，引起有效的体液和细胞介导的免疫反应，独立于疫苗接种途径。我们的结果还表明，JOL1863向鸡单核细胞衍生的树突状细胞（MoDC）传递有效的成熟信号，其特征在于共刺激分子的上调和更高的细胞因子诱导。此外，用JOL1863在鸡中进行免疫接种赋予了针对异源LPAIH7N1病毒攻击的显着保护作用，如泄殖腔拭子中病毒脱落减少所示。我们得出结论，这种疫苗，基于共识HA，可以诱导更广泛的针对不同H7流感病毒的保护，因此值得进一步研究。
