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DNA vaccine protection against SARS-CoV-2 in rhesus macaques.
Science. 2020 08 14; 369(6505):806-811.Sci

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.

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Authors+Show Affiliations

Yu J
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Tostanoski LH
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Peter L
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Mercado NB
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
McMahan K
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Mahrokhian SH
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Nkolola JP
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Liu J
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Li Z
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Chandrashekar A
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Martinez DR
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Loos C
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Atyeo C
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Fischinger S
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Burke JS
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Slein MD
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Chen Y
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Zuiani A
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Lelis FJN
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Travers M
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Habibi S
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Pessaint L
Bioqual, Rockville, MD 20852, USA.
Van Ry A
Bioqual, Rockville, MD 20852, USA.
Blade K
Bioqual, Rockville, MD 20852, USA.
Brown R
Bioqual, Rockville, MD 20852, USA.
Cook A
Bioqual, Rockville, MD 20852, USA.
Finneyfrock B
Bioqual, Rockville, MD 20852, USA.
Dodson A
Bioqual, Rockville, MD 20852, USA.
Teow E
Bioqual, Rockville, MD 20852, USA.
Velasco J
Bioqual, Rockville, MD 20852, USA.
Zahn R
Janssen Vaccines & Prevention BV, Leiden, Netherlands.
Wegmann F
Janssen Vaccines & Prevention BV, Leiden, Netherlands.
Bondzie EA
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Dagotto G
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Gebre MS
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
He X
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Jacob-Dolan C
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Kirilova M
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Kordana N
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Lin Z
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Maxfield LF
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Nampanya F
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Nityanandam R
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Ventura JD
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Wan H
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Cai Y
Children's Hospital, Boston, MA 02115, USA.
Chen B
Children's Hospital, Boston, MA 02115, USA. Massachusetts Consortium on Pathogen Readiness, Boston, MA 02215, USA.
Schmidt AG
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Massachusetts Consortium on Pathogen Readiness, Boston, MA 02215, USA.
Wesemann DR
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Massachusetts Consortium on Pathogen Readiness, Boston, MA 02215, USA.
Baric RS
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Alter G
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Massachusetts Consortium on Pathogen Readiness, Boston, MA 02215, USA.
Andersen H
Bioqual, Rockville, MD 20852, USA.
Lewis MG
Bioqual, Rockville, MD 20852, USA.
Barouch DH
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. dbarouch@bidmc.harvard.edu. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Massachusetts Consortium on Pathogen Readiness, Boston, MA 02215, USA.

MeSH

Adjuvants, ImmunologicAnimalsAntibodies, NeutralizingAntibodies, ViralBetacoronavirusBronchoalveolar Lavage FluidCOVID-19COVID-19 VaccinesCoronavirus InfectionsDisease Models, AnimalFemaleHumansImmunity, CellularImmunity, HumoralImmunization, SecondaryImmunogenicity, VaccineImmunologic MemoryMacaca mulattaMaleMutant ProteinsNasal MucosaPandemicsPneumonia, ViralProtein DomainsSARS-CoV-2Spike Glycoprotein, CoronavirusVaccinationVaccines, DNAViral LoadViral Vaccines

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32434945

Clinical Trial Links

Change in Antibody Levels Following SARS-CoV-2 (Covid-19) Vaccinations

Citation

Yu, Jingyou, et al. "DNA Vaccine Protection Against SARS-CoV-2 in Rhesus Macaques." Science (New York, N.Y.), vol. 369, no. 6505, 2020, pp. 806-811.
Yu J, Tostanoski LH, Peter L, et al. DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science. 2020;369(6505):806-811.
Yu, J., Tostanoski, L. H., Peter, L., Mercado, N. B., McMahan, K., Mahrokhian, S. H., Nkolola, J. P., Liu, J., Li, Z., Chandrashekar, A., Martinez, D. R., Loos, C., Atyeo, C., Fischinger, S., Burke, J. S., Slein, M. D., Chen, Y., Zuiani, A., Lelis, F. J. N., ... Barouch, D. H. (2020). DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science (New York, N.Y.), 369(6505), 806-811. https://doi.org/10.1126/science.abc6284
Yu J, et al. DNA Vaccine Protection Against SARS-CoV-2 in Rhesus Macaques. Science. 2020 08 14;369(6505):806-811. PubMed PMID: 32434945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DNA vaccine protection against SARS-CoV-2 in rhesus macaques. AU - Yu,Jingyou, AU - Tostanoski,Lisa H, AU - Peter,Lauren, AU - Mercado,Noe B, AU - McMahan,Katherine, AU - Mahrokhian,Shant H, AU - Nkolola,Joseph P, AU - Liu,Jinyan, AU - Li,Zhenfeng, AU - Chandrashekar,Abishek, AU - Martinez,David R, AU - Loos,Carolin, AU - Atyeo,Caroline, AU - Fischinger,Stephanie, AU - Burke,John S, AU - Slein,Matthew D, AU - Chen,Yuezhou, AU - Zuiani,Adam, AU - Lelis,Felipe J N, AU - Travers,Meghan, AU - Habibi,Shaghayegh, AU - Pessaint,Laurent, AU - Van Ry,Alex, AU - Blade,Kelvin, AU - Brown,Renita, AU - Cook,Anthony, AU - Finneyfrock,Brad, AU - Dodson,Alan, AU - Teow,Elyse, AU - Velasco,Jason, AU - Zahn,Roland, AU - Wegmann,Frank, AU - Bondzie,Esther A, AU - Dagotto,Gabriel, AU - Gebre,Makda S, AU - He,Xuan, AU - Jacob-Dolan,Catherine, AU - Kirilova,Marinela, AU - Kordana,Nicole, AU - Lin,Zijin, AU - Maxfield,Lori F, AU - Nampanya,Felix, AU - Nityanandam,Ramya, AU - Ventura,John D, AU - Wan,Huahua, AU - Cai,Yongfei, AU - Chen,Bing, AU - Schmidt,Aaron G, AU - Wesemann,Duane R, AU - Baric,Ralph S, AU - Alter,Galit, AU - Andersen,Hanne, AU - Lewis,Mark G, AU - Barouch,Dan H, Y1 - 2020/05/20/ PY - 2020/05/05/received PY - 2020/05/16/accepted PY - 2020/5/22/pubmed PY - 2020/8/28/medline PY - 2020/5/22/entrez SP - 806 EP - 811 JF - Science (New York, N.Y.) JO - Science VL - 369 IS - 6505 N2 - 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. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/32434945/DNA_vaccine_protection_against_SARS_CoV_2_in_rhesus_macaques_ L2 - https://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=32434945 DB - PRIME DP - Unbound Medicine ER -