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SARS-CoV-2 infection protects against rechallenge in rhesus macaques.
Science. 2020 08 14; 369(6505):812-817.Sci

Abstract

An understanding of protective immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for vaccine and public health strategies aimed at ending the global coronavirus disease 2019 (COVID-19) pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against reexposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. After the initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with after the primary infection. Anamnestic immune responses after rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against reexposure in nonhuman primates.

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Authors+Show Affiliations

Chandrashekar A
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.
Martinot AJ
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
McMahan K
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.
Peter L
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.
Yu J
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Maliga Z
Harvard Medical School, Boston, MA 02115, USA.
Nekorchuk M
Oregon Health & Sciences University, Beaverton, OR 97006, USA.
Busman-Sahay K
Oregon Health & Sciences University, Beaverton, OR 97006, USA.
Terry M
Oregon Health & Sciences University, Beaverton, OR 97006, USA.
Wrijil LM
Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Ducat S
Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Martinez DR
University of North Carolina, Chapel Hill, NC 27599, USA.
Atyeo C
Harvard Medical School, Boston, MA 02115, USA. 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.
Pessaint L
Bioqual, Rockville, MD 20852, USA.
Van Ry A
Bioqual, Rockville, MD 20852, USA.
Greenhouse J
Bioqual, Rockville, MD 20852, USA.
Taylor T
Bioqual, Rockville, MD 20852, USA.
Blade K
Bioqual, Rockville, MD 20852, USA.
Cook A
Bioqual, Rockville, MD 20852, USA.
Finneyfrock B
Bioqual, Rockville, MD 20852, USA.
Brown R
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.
Abbink P
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
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. Harvard Medical School, Boston, MA 02115, USA.
Gebre MS
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Harvard Medical School, Boston, MA 02115, 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. Harvard Medical School, Boston, MA 02115, USA.
Kordana N
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.
Lifton MA
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.
Maxfield LF
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.
Nkolola JP
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, 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.
Miller AD
Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
Baric RS
University of North Carolina, 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.
Sorger PK
Harvard Medical School, Boston, MA 02115, USA.
Estes JD
Oregon Health & Sciences University, Beaverton, OR 97006, 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

AnimalsAntibodies, NeutralizingAntibodies, ViralBetacoronavirusBronchoalveolar Lavage FluidCOVID-19Coronavirus InfectionsDisease Models, AnimalFemaleImmunity, CellularImmunity, HumoralImmunologic MemoryLungLung Diseases, InterstitialMacaca mulattaMaleNasal MucosaPandemicsPneumonia, ViralRecurrenceSARS-CoV-2Spike Glycoprotein, CoronavirusViral LoadVirus Replication

Pub Type(s)

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

Language

eng

PubMed ID

32434946

Clinical Trial Links

COVID-19 Antibody Responses In Cystic Fibrosis

Citation

Chandrashekar, Abishek, et al. "SARS-CoV-2 Infection Protects Against Rechallenge in Rhesus Macaques." Science (New York, N.Y.), vol. 369, no. 6505, 2020, pp. 812-817.
Chandrashekar A, Liu J, Martinot AJ, et al. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science. 2020;369(6505):812-817.
Chandrashekar, A., Liu, J., Martinot, A. J., McMahan, K., Mercado, N. B., Peter, L., Tostanoski, L. H., Yu, J., Maliga, Z., Nekorchuk, M., Busman-Sahay, K., Terry, M., Wrijil, L. M., Ducat, S., Martinez, D. R., Atyeo, C., Fischinger, S., Burke, J. S., Slein, M. D., ... Barouch, D. H. (2020). SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science (New York, N.Y.), 369(6505), 812-817. https://doi.org/10.1126/science.abc4776
Chandrashekar A, et al. SARS-CoV-2 Infection Protects Against Rechallenge in Rhesus Macaques. Science. 2020 08 14;369(6505):812-817. PubMed PMID: 32434946.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 infection protects against rechallenge in rhesus macaques. AU - Chandrashekar,Abishek, AU - Liu,Jinyan, AU - Martinot,Amanda J, AU - McMahan,Katherine, AU - Mercado,Noe B, AU - Peter,Lauren, AU - Tostanoski,Lisa H, AU - Yu,Jingyou, AU - Maliga,Zoltan, AU - Nekorchuk,Michael, AU - Busman-Sahay,Kathleen, AU - Terry,Margaret, AU - Wrijil,Linda M, AU - Ducat,Sarah, AU - Martinez,David R, AU - Atyeo,Caroline, AU - Fischinger,Stephanie, AU - Burke,John S, AU - Slein,Matthew D, AU - Pessaint,Laurent, AU - Van Ry,Alex, AU - Greenhouse,Jack, AU - Taylor,Tammy, AU - Blade,Kelvin, AU - Cook,Anthony, AU - Finneyfrock,Brad, AU - Brown,Renita, AU - Teow,Elyse, AU - Velasco,Jason, AU - Zahn,Roland, AU - Wegmann,Frank, AU - Abbink,Peter, AU - Bondzie,Esther A, AU - Dagotto,Gabriel, AU - Gebre,Makda S, AU - He,Xuan, AU - Jacob-Dolan,Catherine, AU - Kordana,Nicole, AU - Li,Zhenfeng, AU - Lifton,Michelle A, AU - Mahrokhian,Shant H, AU - Maxfield,Lori F, AU - Nityanandam,Ramya, AU - Nkolola,Joseph P, AU - Schmidt,Aaron G, AU - Miller,Andrew D, AU - Baric,Ralph S, AU - Alter,Galit, AU - Sorger,Peter K, AU - Estes,Jacob D, AU - Andersen,Hanne, AU - Lewis,Mark G, AU - Barouch,Dan H, Y1 - 2020/05/20/ PY - 2020/04/26/received PY - 2020/05/16/accepted PY - 2020/5/22/pubmed PY - 2020/8/28/medline PY - 2020/5/22/entrez SP - 812 EP - 817 JF - Science (New York, N.Y.) JO - Science VL - 369 IS - 6505 N2 - An understanding of protective immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for vaccine and public health strategies aimed at ending the global coronavirus disease 2019 (COVID-19) pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against reexposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. After the initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with after the primary infection. Anamnestic immune responses after rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against reexposure in nonhuman primates. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/32434946/full_citation DB - PRIME DP - Unbound Medicine ER -