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A DNA Vaccine That Targets Hemagglutinin to Antigen-Presenting Cells Protects Mice against H7 Influenza
Journal of Virology ( IF 5.4 ) Pub Date : 2017-12-01 , DOI: 10.1128/jvi.01340-17
Tor Kristian Andersen 1, 2 , Fan Zhou 1, 3 , Rebecca Cox 1, 3, 4 , Bjarne Bogen 1, 2, 5 , Gunnveig Grødeland 1, 2
Affiliation  

Zoonotic influenza H7 viral infections have a case fatality rate of about 40%. Currently, no or limited human to human spread has occurred, but we may be facing a severe pandemic threat if the virus acquires the ability to transmit between humans. Novel vaccines that can be rapidly produced for global distribution are urgently needed, and DNA vaccines may be the only type of vaccine that allows for the speed necessary to quench an emerging pandemic. Here, we constructed DNA vaccines encoding the hemagglutinin (HA) from influenza A/chicken/Italy/13474/99 (H7N1). In order to increase the efficacy of DNA vaccination, HA was targeted to either major histocompatibility complex class II molecules or chemokine receptors 1, 3, and 5 (CCR1/3/5) that are expressed on antigen-presenting cells (APC). A single DNA vaccination with APC-targeted HA significantly increased antibody levels in sera compared to nontargeted control vaccines. The antibodies were confirmed neutralizing in an H7 pseudotype-based neutralization assay. Furthermore, the APC-targeted vaccines increased the levels of antigen-specific cytotoxic T cells, and a single DNA vaccination could confer protection against a lethal challenge with influenza A/turkey/Italy/3889/1999 (H7N1) in mice. In conclusion, we have developed a vaccine that rapidly could contribute protection against a pandemic threat from avian influenza.

IMPORTANCE Highly pathogenic avian influenza H7 constitute a pandemic threat that can cause severe illness and death in infected individuals. Vaccination is the main method of prophylaxis against influenza, but current vaccine strategies fall short in a pandemic situation due to a prolonged production time and insufficient production capabilities. In contrast, a DNA vaccine can be rapidly produced and deployed to prevent the potential escalation of a highly pathogenic influenza pandemic. We here demonstrate that a single DNA delivery of hemagglutinin from an H7 influenza could mediate full protection against a lethal challenge with H7N1 influenza in mice. Vaccine efficacy was contingent on targeting of the secreted vaccine protein to antigen-presenting cells.



中文翻译:

将血凝素靶向抗原呈递细胞的DNA疫苗可保护小鼠免受H7流感的侵害。

人畜共患的H7流感病毒感染的病死率约为40%。目前,还没有发生或只有有限的人与人之间的传播,但是如果病毒获得了在人与人之间传播的能力,我们可能会面临严重的大流行威胁。迫切需要能够快速生产以供全球分销的新型疫苗,而DNA疫苗可能是唯一一种能够消除突发性大流行所必需的速度的疫苗。在这里,我们构建了编码来自甲型流感/鸡/意大利/ 13474/99(H7N1)的血凝素(HA)的DNA疫苗。为了提高DNA疫苗接种的效力,HA靶向了主要的组织相容性复合物II类分子或在抗原呈递细胞(APC)上表达的趋化因子受体1、3和5(CCR1 / 3/5)。与非靶向对照疫苗相比,以APC靶向HA的单次DNA疫苗接种显着提高了血清中的抗体水平。在基于H7假型的中和测定中证实抗体已被中和。此外,针对APC的疫苗增加了抗原特异性细胞毒性T细胞的水平,单次DNA疫苗接种可以赋予小鼠抗A /火鸡/意大利/ 3889/1999(H7N1)流感致死性攻击的保护作用。总而言之,我们开发了一种疫苗,可以迅速为预防禽流感造成的大流行威胁做出贡献。并且一次DNA疫苗接种可以赋予小鼠抗A型/土耳其/意大利/ 3889/1999(H7N1)流感病毒致死性攻击的保护作用。总而言之,我们开发了一种疫苗,可以迅速为预防禽流感造成的大流行威胁做出贡献。并且一次DNA疫苗接种可以赋予小鼠抗A型/土耳其/意大利/ 3889/1999(H7N1)流感病毒致死性攻击的保护作用。总而言之,我们开发了一种疫苗,可以迅速为预防禽流感造成的大流行威胁做出贡献。

重要信息高致病性禽流感H7构成了大流行性威胁,可能在感染的个人中引起严重的疾病和死亡。疫苗接种是预防流感的主要方法,但由于生产时间延长和生产能力不足,当前的疫苗策略在大流行情况下还不够。相反,DNA疫苗可以快速生产和部署,以防止高致病性流感大流行的潜在升级。我们在这里证明,H7流感病毒的单个DNA血凝素传递可以介导针对小鼠H7N1流感病毒的致死性攻击的全面保护。疫苗效力取决于分泌的疫苗蛋白靶向抗原呈递细胞。

更新日期:2017-11-15
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