DNA vaccine protection against SARS-CoV-2 in rhesus macaques-Reference-Cited by-同舟云学术

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

Published:2020-05-20 Issue:6505 Volume:369 Page:806-811
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Yu Jingyou¹^ORCID,Tostanoski Lisa H.¹^ORCID,Peter Lauren¹^ORCID,Mercado Noe B.¹^ORCID,McMahan Katherine¹^ORCID,Mahrokhian Shant H.¹^ORCID,Nkolola Joseph P.¹^ORCID,Liu Jinyan¹^ORCID,Li Zhenfeng¹,Chandrashekar Abishek¹^ORCID,Martinez David R.²,Loos Carolin³^ORCID,Atyeo Caroline³^ORCID,Fischinger Stephanie³^ORCID,Burke John S.³^ORCID,Slein Matthew D.³^ORCID,Chen Yuezhou⁴,Zuiani Adam⁴^ORCID,Lelis Felipe J. N.⁴^ORCID,Travers Meghan⁴,Habibi Shaghayegh⁴^ORCID,Pessaint Laurent⁵^ORCID,Van Ry Alex⁵^ORCID,Blade Kelvin⁵^ORCID,Brown Renita⁵,Cook Anthony⁵,Finneyfrock Brad⁵^ORCID,Dodson Alan⁵^ORCID,Teow Elyse⁵,Velasco Jason⁵,Zahn Roland⁶^ORCID,Wegmann Frank⁶^ORCID,Bondzie Esther A.¹^ORCID,Dagotto Gabriel¹^ORCID,Gebre Makda S.¹^ORCID,He Xuan¹,Jacob-Dolan Catherine¹^ORCID,Kirilova Marinela¹,Kordana Nicole¹^ORCID,Lin Zijin¹,Maxfield Lori F.¹^ORCID,Nampanya Felix¹,Nityanandam Ramya¹^ORCID,Ventura John D.¹^ORCID,Wan Huahua¹^ORCID,Cai Yongfei⁷^ORCID,Chen Bing⁷⁸^ORCID,Schmidt Aaron G.³⁸^ORCID,Wesemann Duane R.⁴⁸^ORCID,Baric Ralph S.²^ORCID,Alter Galit³⁸^ORCID,Andersen Hanne⁵^ORCID,Lewis Mark G.⁵^ORCID,Barouch Dan H.¹³⁸^ORCID

Affiliation:

1. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

2. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

3. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

4. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

5. Bioqual, Rockville, MD 20852, USA.

6. Janssen Vaccines & Prevention BV, Leiden, Netherlands.

7. Children’s Hospital, Boston, MA 02115, USA.

8. Massachusetts Consortium on Pathogen Readiness, Boston, MA 02215, USA.

Abstract

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 log10 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.

Funder

National Institutes of Health

Burroughs Wellcome Fund

Beth Israel Deaconess Medical Center

Ragon Institute of MGH, MIT, and Harvard

Mark and Lisa Schwartz Foundation

Massachusetts Consortium on Pathogen Readiness

Janssen Vaccines and Prevention BV

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary