SARS-CoV-2 infection protects against rechallenge in rhesus macaques

Abishek Chandrashekar; Jinyan Liu; Amanda J. Martino; Katherine McMahan; Noe B. Mercad; Lauren Peter; Lisa H. Tostanosk; Jingyou Yu; Zoltan Maliga; Michael Nekorchuk; Kathleen Busman-Sahay; Margaret Terry; Linda M. Wriji; Sarah Ducat; David R. Martine; Caroline Atyeo; Stephanie Fischinger; John S. Burk; Matthew D. Slei; Laurent Pessaint; Alex Van Ry; Jack Greenhouse; Tammy Taylor; Kelvin Blade; Anthony Cook; Brad Finneyfrock; Renita Brown; Elyse Teow; Jason Velasco; Roland Zahn; Frank Wegmann; Peter Abbink; Esther A. Bondzi; Gabriel Dagotto; Makda S. Gebr; Xuan He; Catherine Jacob-Dolan; Nicole Kordana; Zhenfeng Li; Michelle A. Lifto; Shant H. Mahrokhia; Lori F. Maxfiel; Ramya Nityanandam; Joseph P. Nkolol; Aaron G. Schmid; Andrew D. Mille; Ralph S. Bari; Galit Alter; Peter K. Sorge; Jacob D. Este; Hanne Andersen; Mark G. Lewi; Dan H. Barou

doi:10.1126/science.abc4776

SARS-CoV-2 infection protects against rechallenge in rhesus macaques

Abishek Chandrashekar, Jinyan Liu, Amanda J. Martino, Katherine McMahan, Noe B. Mercad, Lauren Peter, Lisa H. Tostanosk, Jingyou Yu, Zoltan Maliga, Michael Nekorchuk, Kathleen Busman-Sahay, Margaret Terry, Linda M. Wriji, Sarah Ducat, David R. Martine, Caroline Atyeo, Stephanie Fischinger, John S. Burk, Matthew D. Slei, Laurent PessaintAlex Van Ry, Jack Greenhouse, Tammy Taylor, Kelvin Blade, Anthony Cook, Brad Finneyfrock, Renita Brown, Elyse Teow, Jason Velasco, Roland Zahn, Frank Wegmann, Peter Abbink, Esther A. Bondzi, Gabriel Dagotto, Makda S. Gebr, Xuan He, Catherine Jacob-Dolan, Nicole Kordana, Zhenfeng Li, Michelle A. Lifto, Shant H. Mahrokhia, Lori F. Maxfiel, Ramya Nityanandam, Joseph P. Nkolol, Aaron G. Schmid, Andrew D. Mille, Ralph S. Bari, Galit Alter, Peter K. Sorge, Jacob D. Este, Hanne Andersen, Mark G. Lewi, Dan H. Barou

Vaccine and Gene Therapy Institute

Research output: Contribution to journal › Article › peer-review

627 Scopus citations

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.

Original language	English (US)
Pages (from-to)	812-817
Number of pages	6
Journal	Science
Volume	369
Issue number	6505
DOIs	https://doi.org/10.1126/science.abc4776
State	Published - Aug 14 2020

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Chandrashekar, A., Liu, J., Martino, A. J., McMahan, K., Mercad, N. B., Peter, L., Tostanosk, L. H., Yu, J., Maliga, Z., Nekorchuk, M., Busman-Sahay, K., Terry, M., Wriji, L. M., Ducat, S., Martine, D. R., Atyeo, C., Fischinger, S., Burk, J. S., Slei, M. D., ... Barou, D. H. (2020). SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science, 369(6505), 812-817. https://doi.org/10.1126/science.abc4776

Chandrashekar, A, Liu, J, Martino, AJ, McMahan, K, Mercad, NB, Peter, L, Tostanosk, LH, Yu, J, Maliga, Z, Nekorchuk, M, Busman-Sahay, K, Terry, M, Wriji, LM, Ducat, S, Martine, DR, Atyeo, C, Fischinger, S, Burk, JS, Slei, MD, Pessaint, L, Van Ry, A, Greenhouse, J, Taylor, T, Blade, K, Cook, A, Finneyfrock, B, Brown, R, Teow, E, Velasco, J, Zahn, R, Wegmann, F, Abbink, P, Bondzi, EA, Dagotto, G, Gebr, MS, He, X, Jacob-Dolan, C, Kordana, N, Li, Z, Lifto, MA, Mahrokhia, SH, Maxfiel, LF, Nityanandam, R, Nkolol, JP, Schmid, AG, Mille, AD, Bari, RS, Alter, G, Sorge, PK, Este, JD, Andersen, H, Lewi, MG & Barou, DH 2020, 'SARS-CoV-2 infection protects against rechallenge in rhesus macaques', Science, vol. 369, no. 6505, pp. 812-817. https://doi.org/10.1126/science.abc4776

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title = "SARS-CoV-2 infection protects against rechallenge in rhesus macaques",

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.",

author = "Abishek Chandrashekar and Jinyan Liu and Martino, {Amanda J.} and Katherine McMahan and Mercad, {Noe B.} and Lauren Peter and Tostanosk, {Lisa H.} and Jingyou Yu and Zoltan Maliga and Michael Nekorchuk and Kathleen Busman-Sahay and Margaret Terry and Wriji, {Linda M.} and Sarah Ducat and Martine, {David R.} and Caroline Atyeo and Stephanie Fischinger and Burk, {John S.} and Slei, {Matthew D.} and Laurent Pessaint and {Van Ry}, Alex and Jack Greenhouse and Tammy Taylor and Kelvin Blade and Anthony Cook and Brad Finneyfrock and Renita Brown and Elyse Teow and Jason Velasco and Roland Zahn and Frank Wegmann and Peter Abbink and Bondzi, {Esther A.} and Gabriel Dagotto and Gebr, {Makda S.} and Xuan He and Catherine Jacob-Dolan and Nicole Kordana and Zhenfeng Li and Lifto, {Michelle A.} and Mahrokhia, {Shant H.} and Maxfiel, {Lori F.} and Ramya Nityanandam and Nkolol, {Joseph P.} and Schmid, {Aaron G.} and Mille, {Andrew D.} and Bari, {Ralph S.} and Galit Alter and Sorge, {Peter K.} and Este, {Jacob D.} and Hanne Andersen and Lewi, {Mark G.} and Barou, {Dan H.}",

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doi = "10.1126/science.abc4776",

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T1 - SARS-CoV-2 infection protects against rechallenge in rhesus macaques

AU - Chandrashekar, Abishek

AU - Liu, Jinyan

AU - Martino, Amanda J.

AU - McMahan, Katherine

AU - Mercad, Noe B.

AU - Peter, Lauren

AU - Tostanosk, Lisa H.

AU - Yu, Jingyou

AU - Maliga, Zoltan

AU - Nekorchuk, Michael

AU - Busman-Sahay, Kathleen

AU - Terry, Margaret

AU - Wriji, Linda M.

AU - Ducat, Sarah

AU - Martine, David R.

AU - Atyeo, Caroline

AU - Fischinger, Stephanie

AU - Burk, John S.

AU - Slei, 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 - Bondzi, Esther A.

AU - Dagotto, Gabriel

AU - Gebr, Makda S.

AU - He, Xuan

AU - Jacob-Dolan, Catherine

AU - Kordana, Nicole

AU - Li, Zhenfeng

AU - Lifto, Michelle A.

AU - Mahrokhia, Shant H.

AU - Maxfiel, Lori F.

AU - Nityanandam, Ramya

AU - Nkolol, Joseph P.

AU - Schmid, Aaron G.

AU - Mille, Andrew D.

AU - Bari, Ralph S.

AU - Alter, Galit

AU - Sorge, Peter K.

AU - Este, Jacob D.

AU - Andersen, Hanne

AU - Lewi, Mark G.

AU - Barou, Dan H.

PY - 2020/8/14

Y1 - 2020/8/14

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.

AB - 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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SARS-CoV-2 infection protects against rechallenge in rhesus macaques

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