An Intramuscular DNA Vaccine for SARS-CoV-2 Decreases Viral Lung Load but Not Lung Pathology in Syrian Hamsters.
An Intramuscular DNA Vaccine for SARS-CoV-2 Decreases Viral Lung Load but Not Lung Pathology in Syrian Hamsters.
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DOI：
10.3390/microorganisms9051040
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发表时间：
2021-05-12
期刊：
影响因子：
4.5
通讯作者：
Hawman DW
中科院分区：
文献类型：
--
作者：
Leventhal SS;Clancy C;Erasmus J;Feldmann H;Hawman DW
2019年12月首次报告的2019年新型冠状病毒SARS-CoV-2，截至2021年2月已感染全球超过1.02亿人，因此需要快速开发安全有效的干预措施，即疫苗。在我们的研究中，我们在叙利亚仓鼠模型中评估了针对SARS-CoV-2的DNA疫苗。用编码SARS-CoV-2全长刺突开放阅读框（ORF）的DNA质粒接种仓鼠，以诱导宿主细胞产生刺突蛋白和保护性免疫应答。我们通过鼻内（IN）和肌内（IM）给药途径以及与和不与体内递送试剂复合来测试该候选疫苗。与对照接种动物相比，接受初免-加强-加强IM接种的仓鼠恢复体重更快，肺部病毒载量降低，SARS-CoV-2特异性抗体滴度增加，但令人惊讶的是，肺部病理学与假接种对照一样严重。IM/IN组合组显示在降低肺病毒滴度或病理学方面没有功效。随着公共卫生对快速有效干预的需求日益增加，我们的数据表明，在某些疫苗背景下，显著的抗体应答和病毒载量降低可能不足以预防肺部病变。
The 2019 novel coronavirus, SARS-CoV-2, first reported in December 2019, has infected over 102 million people around the world as of February 2021 and thus calls for rapid development of safe and effective interventions, namely vaccines. In our study, we evaluated a DNA vaccine against SARS-CoV-2 in the Syrian hamster model. Hamsters were vaccinated with a DNA-plasmid encoding the SARS-CoV-2 full length spike open reading frame (ORF) to induce host cells to produce spike protein and protective immune responses before exposure to infectious virus. We tested this vaccine candidate by both intranasal (IN) and intramuscular (IM) routes of administration and complexing with and without an in vivo delivery reagent. Hamsters receiving prime-boost-boost IM-only vaccinations recovered body weight quicker, had decreased lung viral loads, and increased SARS-CoV-2-specific antibody titers compared to control vaccinated animals but, surprisingly, lung pathology was as severe as sham vaccinated controls. The IM/IN combination group showed no efficacy in reducing lung virus titers or pathology. With increasing public health need for rapid and effective interventions, our data demonstrate that in some vaccine contexts, significant antibody responses and decreased viral loads may not be sufficient to prevent lung pathology.
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