Accelerated DNA vaccine regimen provides protection against Crimean-Congo hemorrhagic fever virus challenge in a macaque model.

Accelerated DNA vaccine regimen provides protection against Crimean-Congo hemorrhagic fever virus challenge in a macaque model.
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DOI:
10.1016/j.ymthe.2022.09.016
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发表时间:
2023-02-01
期刊:
影响因子:
12.4
通讯作者:
Feldmann, Heinz
Feldmann, Heinz
中科院分区:
医学1区
文献类型:
--
作者:
Hawman, David W.;Meade-White, Kimberly;Leventhal, Shanna;Appelberg, Sofia;Ahlen, Gustaf;Nikouyan, Negin;Clancy, Chad;Smith, Brian;Hanley, Patrick;Lovaglio, Jamie;Mirazimi, Ali;Sallberg, Matti;Feldmann, Heinz

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克里米亚-刚果出血热病毒(CCHFV)广泛分布于非洲、中东、南亚以及南欧和东欧。CCHF通过透明线虫或接触受感染的动物传播,开始时是非特异性的,但可以迅速发展为严重的,有时是致命的疾病。由于非特定的早期症状和往往无法识别的感染,患者经常出现在医疗系统表现出疾病的后期,当治疗仅限于支持性护理时。因此,迫切需要简单的疫苗来保护有CCHFV感染风险的人群。目前,还没有被广泛批准的CCHFV疫苗。我们之前已经报道了CCHFV的三剂DNA疫苗接种方案对食蟹猴(猕猴)的显著疗效。在这里,我们发现在食蟹猴中,表达的CCHFV核蛋白(NP)和糖蛋白前体(GPC)抗原分别主要诱导体液免疫和细胞免疫。我们发现,表达NP和GPC的两剂疫苗方案对CCHFV感染具有显著的保护作用。对单独使用这两种抗原的疫苗的研究表明,表达质粒的NPs也可以提供保护。总而言之,我们的数据显示,这种疫苗对CCHFV具有强大的保护作用,并表明体液免疫和细胞免疫都有助于疫苗介导的最佳保护。Feldmann和他的同事在非人类灵长类动物模型中评估了一种基于DNA的克里米亚-刚果出血热病毒疫苗,发现两种免疫足以预防感染和疾病。保护与强大但非中和的抗体反应相关。这些数据支持这种候选疫苗的继续开发。
Crimean-Congo hemorrhagic fever virus (CCHFV) is widely distributed throughout Africa, the Middle East, Southern Asia, and Southern and Eastern Europe. Spread by Hyalomma ticks or by contact with infected animals, CCHF begins non-specifically but can rapidly progress to severe, sometimes fatal, disease. Due to the non-specific early symptoms and often unrecognized infections, patients often present to healthcare systems exhibiting later stages of disease, when treatment is limited to supportive care. Consequently, simple vaccines are critically needed to protect populations at risk of CCHFV infection. Currently, there are no widely approved vaccines for CCHFV. We have previously reported significant efficacy of a three-dose DNA-based vaccination regimen for CCHFV in cynomolgus macaques (Macaca fasicularis). Here, we show that in cynomolgus macaques, plasmid-expressed CCHFV nucleoprotein (NP) and glycoprotein precursor (GPC) antigens elicit primarily humoral and cellular immunity, respectively. We found that a two-dose vaccination regimen with plasmids expressing the NP and GPC provides significant protection against CCHFV infection. Studies investigating vaccinations with either antigen alone showed that plasmid-expressed NPs could also confer protection. Cumulatively, our data show that this vaccine confers robust protection against CCHFV and suggest that both humoral and cellular immunity contribute to optimal vaccine-mediated protection. Feldmann and colleagues have evaluated a DNA-based vaccine for Crimean-Congo hemorrhagic fever virus in a non-human primate model and found that two immunizations were sufficient to protect against infection and disease. Protection correlated with a robust, but non-neutralizing, antibody response. These data support continued development of this vaccine candidate.
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