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

被引：767

作者：

Yu, Jingyou ^{[1
]}

Tostanoski, Lisa H. ^{[1
]}

Peter, Lauren ^{[1
]}

Mercado, Noe B. ^{[1
]}

McMahan, Katherine ^{[1
]}

Mahrokhian, Shant H. ^{[1
]}

Nkolola, Joseph P. ^{[1
]}

Liu, Jinyan ^{[1
]}

Li, Zhenfeng ^{[1
]}

Chandrashekar, Abishek ^{[1
]}

Martinez, David R. ^{[2
]}

Loos, Carolin ^{[3
,4
]}

Atyeo, Caroline ^{[3
,4
]}

Fischinger, Stephanie ^{[3
,4
]}

Burke, John S. ^{[3
,4
]}

Slein, Matthew D. ^{[3
,4
]}

Chen, Yuezhou ^{[5
]}

Zuiani, Adam ^{[5
]}

Lelis, Felipe J. N. ^{[5
]}

Travers, Meghan ^{[5
]}

Habibi, Shaghayegh ^{[5
]}

Pessaint, Laurent ^{[6
]}

Van Ry, Alex ^{[6
]}

Blade, Kelvin ^{[6
]}

Brown, Renita ^{[6
]}

Cook, Anthony ^{[6
]}

Finneyfrock, Brad ^{[6
]}

Dodson, Alan ^{[6
]}

Teow, Elyse ^{[6
]}

Velasco, Jason ^{[6
]}

Zahn, Roland ^{[7
]}

Wegmann, Frank ^{[7
]}

Bondzie, Esther A. ^{[1
]}

Dagotto, Gabriel ^{[1
]}

Gebre, Makda S. ^{[1
]}

He, Xuan ^{[1
]}

Jacob-Dolan, Catherine ^{[1
]}

Kirilova, Marinela ^{[1
]}

Kordana, Nicole ^{[1
]}

Lin, Zijin ^{[1
]}

Maxfield, Lori F. ^{[1
]}

Nampanya, Felix ^{[1
]}

Nityanandam, Ramya ^{[1
]}

Ventura, John D. ^{[1
]}

Wan, Huahua ^{[1
]}

Cai, Yongfei ^{[8
]}

Chen, Bing ^{[8
,9
]}

Schmidt, Aaron G. ^{[3
,4
,9
]}

Wesemann, Duane R. ^{[5
,9
]}

Baric, Ralph S. ^{[2
]}

机构：

[1] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA

[2] Univ North Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA

[3] MIT, Ragon Inst MGH, Cambridge, MA 02139 USA

[4] Harvard, Cambridge, MA 02139 USA

[5] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA

[6] Bioqual, Rockville, MD 20852 USA

[7] Janssen Vaccines & Prevent BV, Leiden, Netherlands

[8] Childrens Hosp, Boston, MA 02115 USA

[9] Massachusetts Consortium Pathogen Readiness, Boston, MA 02215 USA

来源：

SCIENCE | 2020年 / 369卷 / 6505期

基金：

美国国家卫生研究院;

关键词：

LENGTH INFECTIOUS CDNA; NEUTRALIZING ANTIBODY; SARS CORONAVIRUS; REVERSE GENETICS; IMMUNE-RESPONSES; EFFICACY; SPIKE;

D O I：

10.1126/science.abc6284

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：806 / +

页数：37

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