DNA vaccine protection against SARS-CoV-2 in rhesus macaques

DNA vaccine protection against SARS-CoV-2 in rhesus macaques
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DOI:
10.1126/science.abc6284
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发表时间:
2020-08-14
期刊:
影响因子:
56.9
通讯作者:
Barouch, Dan H.
Barouch, Dan H.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Yu, Jingyou;Tostanoski, Lisa H.;Barouch, Dan H.

文献摘要

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由严重急性呼吸道综合征冠状病毒2型(SARS-CoV-2)引起的2019年全球冠状病毒病(COVID-19)大流行使疫苗的开发成为生物医学的首要任务。在这项研究中,我们开发了一系列表达不同形式的SARS-CoV- 2刺突(S)蛋白的DNA疫苗候选物,并在35只恒河猴中进行了评估。接种疫苗的动物产生了体液和细胞免疫应答,包括中和抗体滴度,其水平与感染SARS-CoV-2的康复期人类和猕猴相当。接种疫苗后,所有动物均用SARS-CoV-2攻击,与假手术对照组的病毒载量相比,编码全长S蛋白的疫苗导致支气管肺泡灌洗液和鼻粘膜中的中值病毒载量分别降低>3.1和>3.7 log(10)。疫苗引起的中和抗体滴度与保护效力相关,表明保护的免疫相关性。这些数据证明了疫苗在非人灵长类动物中对SARS-CoV-2的保护作用。
The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV- 2 spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. After vaccination, all animals were challenged with SARS- CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with viral loads in sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.