Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Science. 2020 Aug 14;369(6505):806-811. doi: 10.1126/science.abc6284. Epub 2020 May 20.
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 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.
由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起的全球 2019 年冠状病毒病(COVID-19)大流行使得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,包括中和抗体滴度可与康复期人类和感染 SARS-CoV-2 的恒河猴相当。接种疫苗后,所有动物均用 SARS-CoV-2 进行攻毒,编码全长 S 蛋白的疫苗分别使支气管肺泡灌洗液和鼻黏膜中的中位病毒载量降低了>3.1 和>3.7 对数,与假疫苗对照相比。疫苗诱导的中和抗体滴度与保护效力相关,提示存在保护的免疫相关性。这些数据表明疫苗可预防 SARS-CoV-2 在非人类灵长类动物中的感染。