Replicating bacterium-vectored vaccine expressing SARS-CoV-2 Membrane and Nucleocapsid proteins protects against severe COVID-19-like disease in hamsters.

Replicating bacterium-vectored vaccine expressing SARS-CoV-2 Membrane and Nucleocapsid proteins protects against severe COVID-19-like disease in hamsters.
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DOI:
10.1038/s41541-021-00321-8
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发表时间:
2021-03-30
期刊:
影响因子:
9.2
通讯作者:
Horwitz MA
Horwitz MA
中科院分区:
医学1区
文献类型:
--
作者:
Jia Q;Bielefeldt-Ohmann H;Maison RM;Masleša-Galić S;Cooper SK;Bowen RA;Horwitz MA

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为了产生廉价的易于制造的COVID-19疫苗,我们采用了LVS ΔcapB载体平台,该平台先前用于产生针对选择性病原体疾病兔热病、炭疽、鼠疫和类鼻疽的有效候选疫苗。表达SARS-CoV-2结构蛋白的疫苗是使用LVS ΔcapB载体(一种高度减毒的细胞内复制细菌)构建的,并评估了对叙利亚金仓鼠的功效,这些仓鼠会患上严重的COVID-19样疾病。用共表达膜蛋白和核衣壳蛋白的疫苗皮内或鼻内免疫并在5周后用高剂量SARS-CoV-2攻击的仓鼠被保护免于严重的体重减轻和肺部病理,并显示口咽和肺部的病毒载量减少。保护作用与抗核衣壳抗体相关。这种有效的疫苗应该是安全的;便宜的;容易制造、储存和分发;并且鉴于SARS-CoV和SARS-CoV-2的膜和核衣壳蛋白之间的高度同源性,可能用作针对引起大流行的β-冠状病毒的SARS子集的通用疫苗。
To generate an inexpensive readily manufactured COVID-19 vaccine, we employed the LVS ΔcapB vector platform, previously used to generate potent candidate vaccines against Select Agent diseases tularemia, anthrax, plague, and melioidosis. Vaccines expressing SARS-CoV-2 structural proteins are constructed using the LVS ΔcapB vector, a highly attenuated replicating intracellular bacterium, and evaluated for efficacy in golden Syrian hamsters, which develop severe COVID-19-like disease. Hamsters immunized intradermally or intranasally with a vaccine co-expressing the Membrane and Nucleocapsid proteins and challenged 5 weeks later with a high dose of SARS-CoV-2 are protected against severe weight loss and lung pathology and show reduced viral loads in the oropharynx and lungs. Protection correlates with anti-Nucleocapsid antibody. This potent vaccine should be safe; inexpensive; easily manufactured, stored, and distributed; and given the high homology between Membrane and Nucleocapsid proteins of SARS-CoV and SARS-CoV-2, potentially serve as a universal vaccine against the SARS subset of pandemic causing β-coronaviruses.
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