首页> 外文会议>Conference on vaccine technology VI >VACCINATION WITH VIRAL VECTORS EXPRESSING NP, M1 AND CHIMERIC HEMAGGLUTININ INDUCES BROAD PROTECTION AGAINST INFLUENZA VIRUS CHALLENGE IN MICE
【24h】

VACCINATION WITH VIRAL VECTORS EXPRESSING NP, M1 AND CHIMERIC HEMAGGLUTININ INDUCES BROAD PROTECTION AGAINST INFLUENZA VIRUS CHALLENGE IN MICE

机译:用表达NP,M1和嵌合血凝素的病毒载体接种疫苗可预防小鼠的流感病毒感染

获取原文

摘要

Seasonal influenza virus infections cause up to half a million deaths each year, the majority of which are older adults. Annual influenza virus vaccination protects against disease, but in the event of a mismatch between the circulating strain and vaccine strain, vaccine effectiveness is severely impacted. Therefore, there is an urgent need for a vaccine that induces broad protection against drifted seasonal and emerging pandemic influenza viruses. One approach in designing such a universal influenza virus vaccine is based on targeting conserved regions of the influenza virus hemagglutinin (HA), the major glycoprotein on the surface of the virus. Using chimeric hemagglutinin constructs (cHA), the immune system can be primed to produce antibody responses against the conserved immunosubdominant stalk region rather than the variable immunodominant head region. Furthermore, replication deficient viral vectors based on Chimpanzee Adenovirus (ChAdOxl) and Modified Vaccinia Ankara (MVA) virus expressing the influenza virus internal antigens, such as the nucleoprotein (NP) and the matrix protein 1 (M1), are capable of inducing strong influenza specific T cell responses in vaccinated individuals. This is another approach towards a broadly cross-protective influenza vaccine given the degree of conservation of NP and M1 across different influenza virus strains. Here, we combine these two platforms to evaluate the efficacy of a viral vector-based group 2 cHA intramuscular vaccination regime in mice to confer protection against influenza virus challenge of matched and mismatched group 2 strains. We show that vectored vaccines expressing both cHA and an NP-M1 fusion protein, in a prime-boost regimen (with different cHAs given at each vaccination), provide enhanced protection against H3N2 and H10N8 virus challenge when compared to vaccination with cHA alone or NP-M1 alone. The vaccine induced antibody responses against divergent HAs, NP, M1, and whole virus correlated with nature of administered vaccine and extent of protection seen across vaccinated groups. Influenza specific T cell responses were also increased in the vectored vaccines expressing both the cHA and the NP-M1 fusion protein. For further characterization, we are interested in looking at an optimal vaccination regimen, the possibility of an additional boost to induce cross-reactive antibodies, and the nature of the induced antibodies. Overall, these results improve our understanding of vaccination platforms capable of harnessing cellular and humoral immunity with the ultimate goal of designing a universal influenza vaccine.
机译:季节性流感病毒感染每年导致多达50万人死亡,其中大多数是老年人。每年进行流感病毒疫苗接种可预防疾病,但是如果循环株与疫苗株之间不匹配,则会严重影响疫苗的有效性。因此,迫切需要一种能够针对季节性和新兴大流行流感病毒引起广泛保护的疫苗。设计这种通用流感病毒疫苗的一种方法是基于靶向流感病毒血凝素(HA)的保守区域,该区域是病毒表面的主要糖蛋白。使用嵌合血凝素构建体(cHA),可以启动免疫系统以产生针对保守的免疫优势茎区域而非可变免疫优势头部区域的抗体反应。此外,基于黑猩猩腺病毒(ChAdOxl)和表达流感病毒内部抗原(如核蛋白(NP)和基质蛋白1(M1))的改良痘苗安卡拉(MVA)病毒的复制缺陷型病毒载体能够诱导强流感疫苗接种个体中的特异性T细胞反应。考虑到NP和M1在不同流感病毒株之间的保守程度,这是一种广泛交叉保护性流感疫苗的另一种方法。在这里,我们结合这两个平台,以评估基于病毒载体的第2组cHA肌肉内疫苗接种方案在小鼠中的作用,以提供针对匹配和错配的第2株流感病毒攻击的保护作用。我们显示,在初免-加强方案中(每次接种均给予不同的cHAs),表达cHA和NP-M1融合蛋白的载体化疫苗与单独接种cHA或NP相比,可增强针对H3N2和H10N8病毒攻击的保护-M1。疫苗诱导的针对不同的HA,NP,M1和整个病毒的抗体反应与疫苗接种的性质以及跨接种组的保护程度有关。在同时表达cHA和NP-M1融合蛋白的载体疫苗中,流感特异性T细胞反应也增加了。为了进一步表征,我们感兴趣的是寻找最佳的疫苗接种方案,进一步加强免疫以诱导交叉反应性抗体的可能性以及所诱导抗体的性质。总体而言,这些结果改善了我们对能够利用细胞和体液免疫力的疫苗接种平台的理解,从而最终设计出通用的流感疫苗。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号