A novel approach for developing inactivated chikungunya virus vaccine

基孔肯雅病毒(Chikungenya Virus，CHIKV)是一种新出现的传染病病毒，已造成大规模的 过去十年的疫情，其中一些仍在继续。长达十年的基孔肯雅病的代价 疫情爆发，包括医疗和生产力损失，价值数十亿美元。没有 获得许可的CHIKV疫苗或针对CHIKV的特定治疗药物。美国陆军曾 开发了CHIKV减毒活毒株CHIKV181/25，尽管展示了 良好的免疫原性在临床试验中失败，因为在一些病毒中残留毒力 接种疫苗的人。在其他一些病例中，残留毒力也有类似的结果。 甲型病毒减毒疫苗候选疫苗。因此，这是不可能的一个活体衰减 甲型病毒将获得FDA批准作为人类应用的疫苗。人们重新关注…… 产生灭活或高度减毒的嵌合CHIKV候选疫苗。在这项研究中，一个 用于生产γ辐射灭活疫苗的新方法将被测试为γ辐射。 假设将首先通过评估CHIKV在细胞培养中的完全失活来检验， 和在敏感新生小鼠体内，从而排除CHIKV对CHIKV感染性的保护作用 γ照射期间的亚甲基二磷酸核苷复合体。灭活CHIKV的表位完整性 将使用针对病毒包膜糖蛋白的单抗进行评估。 在诱导抗CHIKV抗体方面的免疫原性潜力将在#年评估 免疫活性C57BL6小鼠。灭活CHIKV的保护效果将在以下方面进行评估- 体内建立成年A129(干扰素α/βR-/-)小鼠CHIKV感染模型。单一免疫潜力 也将对灭活的CHIKV进行评估。CHIKV感染在一年内迅速传播 疫情爆发。单一免疫将导致更短的时间，从而更好地坚持免疫 发展对病毒的保护性免疫所需的方案，并将有助于 抗击寨卡病毒暴发的爆炸性。拟议研究的长期目标是 开发一种安全有效的CHIKV候选疫苗。目前正在发生的寨卡病毒疫情 已经显示出有可能蔓延到地球上以前的天真地区，如 北美洲。在缺乏有效的抗CHIKV药物、疫苗和任何群体免疫的情况下 它的人口，在毗邻的北美洲爆发的奇卡病毒将是毁灭性的。

Chikungunya virus (CHIKV) is an emerging infectious disease virus that has caused large scale outbreaks in the last decade, some of these are ongoing. The cost of decade long chikungunya outbreak, including medical and productivity loss, runs in billions of dollars. There are no licensed CHIKV vaccine or specific threapeutic drugs against CHIKV. United States Army had developed a live attenuated strain of CHIKV, CHIKV181/25, which in spite of demonstrating excellent immunogenicity failed in clinical trials due to residual virulence in some of the vaccinees. Similar outcome of residual virulence has also been reported in some other cases of attenuated alphavirus vaccine candidates. Therefore, it is unlikely that a live attenuated alphavirus will get FDA approval as vaccine for human application. There is a renewed focus on generating inactivated or highly attenuated chimeric CHIKV vaccine candidates. In this study, a novel approach for generating γ-radiation-inactivated CHIKV vaccine will be tested γ-radiation. Hypothesis will be tested first by evaluating the complete inactivation of CHIKV in cell culture, and in-vivo in sensitive neonatal mice, so as to rule out the protection of infectivity of CHIKV by MDP complex during exposure with γ-radiation. Second, epitope integrity of inactivated CHIKV will be evaluated using monoclonal antibodies against the virus envelope glycoproteins. Immunogenic potential in terms of induction of anti-CHIKV antibody will be evaluated in immunocompetent C57BL6 mice. Protective efficacy of inactivated CHIKV will be evaluated in- vivo in adult A129 (IFNα/βR-/-) mice model of CHIKV infection. Single immunization potential of inactivated CHIKV will also be evaluated. CHIKV infections spread rapidly during an outbreak. Single immunization will result in short and thereby, better adherence to immunization regimen that would be needed to develop protective immunivty against the virus, and will help in fighting the explosive nature of CHIKV outbreak. Long-term goal of the proposed research is to develop a safe and effective CHIKV-vaccine candidate. The current ongoing outbreak of CHIKV has shown potential to spread to the previously CHIKV-naïve regions of the globe such as the North Americas. In absence of an effective anti-CHIKV drug, vaccine, and any herd immunity in its population, CHIKV outbreak in the contiguous North Americas will be devastating.