Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

Lisa H. Tostanoski; Frank Wegmann; Amanda J. Martinot; Carolin Loos; Katherine McMahan; Noe B. Mercado; Jingyou Yu; Chi N. Chan; Stephen Bondoc; Carly E. Starke; Michael Nekorchuk; Kathleen Busman-Sahay; Cesar Piedra-Mora; Linda M. Wrijil; Sarah Ducat; Jerome Custers; Caroline Atyeo; Stephanie Fischinger; John S. Burke; Jared Feldman; Blake M. Hauser; Timothy M. Caradonna; Esther A. Bondzie; Gabriel Dagotto; Makda S. Gebre; Catherine Jacob-Dolan; Zijin Lin; Shant H. Mahrokhian; Felix Nampanya; Ramya Nityanandam; Laurent Pessaint; Maciel Porto; Vaneesha Ali; Dalia Benetiene; Komlan Tevi; Hanne Andersen; Mark G. Lewis; Aaron G. Schmidt; Douglas A. Lauffenburger; Galit Alter; Jacob D. Estes; Hanneke Schuitemaker; Roland Zahn; Dan H. Barouch

doi:10.1038/s41591-020-1070-6

Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

Lisa H. Tostanoski, Frank Wegmann, Amanda J. Martinot, Carolin Loos, Katherine McMahan, Noe B. Mercado, Jingyou Yu, Chi N. Chan, Stephen Bondoc, Carly E. Starke, Michael Nekorchuk, Kathleen Busman-Sahay, Cesar Piedra-Mora, Linda M. Wrijil, Sarah Ducat, Jerome Custers, Caroline Atyeo, Stephanie Fischinger, John S. Burke, Jared FeldmanBlake M. Hauser, Timothy M. Caradonna, Esther A. Bondzie, Gabriel Dagotto, Makda S. Gebre, Catherine Jacob-Dolan, Zijin Lin, Shant H. Mahrokhian, Felix Nampanya, Ramya Nityanandam, Laurent Pessaint, Maciel Porto, Vaneesha Ali, Dalia Benetiene, Komlan Tevi, Hanne Andersen, Mark G. Lewis, Aaron G. Schmidt, Douglas A. Lauffenburger, Galit Alter, Jacob D. Estes, Hanneke Schuitemaker, Roland Zahn, Dan H. Barouch

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

216 Scopus citations

Abstract

Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death^1–4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters^5–7 and nonhuman primates^8–10 have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates^11–13. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.

Original language	English (US)
Pages (from-to)	1694-1700
Number of pages	7
Journal	Nature medicine
Volume	26
Issue number	11
DOIs	https://doi.org/10.1038/s41591-020-1070-6
State	Published - Nov 2020

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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Tostanoski, L. H., Wegmann, F., Martinot, A. J., Loos, C., McMahan, K., Mercado, N. B., Yu, J., Chan, C. N., Bondoc, S., Starke, C. E., Nekorchuk, M., Busman-Sahay, K., Piedra-Mora, C., Wrijil, L. M., Ducat, S., Custers, J., Atyeo, C., Fischinger, S., Burke, J. S., ... Barouch, D. H. (2020). Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters. Nature medicine, 26(11), 1694-1700. https://doi.org/10.1038/s41591-020-1070-6

Tostanoski, LH, Wegmann, F, Martinot, AJ, Loos, C, McMahan, K, Mercado, NB, Yu, J, Chan, CN, Bondoc, S, Starke, CE, Nekorchuk, M , Busman-Sahay, K, Piedra-Mora, C, Wrijil, LM, Ducat, S, Custers, J, Atyeo, C, Fischinger, S, Burke, JS, Feldman, J, Hauser, BM, Caradonna, TM, Bondzie, EA, Dagotto, G, Gebre, MS, Jacob-Dolan, C, Lin, Z, Mahrokhian, SH, Nampanya, F, Nityanandam, R, Pessaint, L, Porto, M, Ali, V, Benetiene, D, Tevi, K, Andersen, H, Lewis, MG, Schmidt, AG, Lauffenburger, DA, Alter, G, Estes, JD, Schuitemaker, H, Zahn, R & Barouch, DH 2020, 'Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters', Nature medicine, vol. 26, no. 11, pp. 1694-1700. https://doi.org/10.1038/s41591-020-1070-6

@article{b226a2d3b2a7483788a64c000dd576b0,

title = "Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters",

abstract = "Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death1–4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters5–7 and nonhuman primates8–10 have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates11–13. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.",

author = "Tostanoski, {Lisa H.} and Frank Wegmann and Martinot, {Amanda J.} and Carolin Loos and Katherine McMahan and Mercado, {Noe B.} and Jingyou Yu and Chan, {Chi N.} and Stephen Bondoc and Starke, {Carly E.} and Michael Nekorchuk and Kathleen Busman-Sahay and Cesar Piedra-Mora and Wrijil, {Linda M.} and Sarah Ducat and Jerome Custers and Caroline Atyeo and Stephanie Fischinger and Burke, {John S.} and Jared Feldman and Hauser, {Blake M.} and Caradonna, {Timothy M.} and Bondzie, {Esther A.} and Gabriel Dagotto and Gebre, {Makda S.} and Catherine Jacob-Dolan and Zijin Lin and Mahrokhian, {Shant H.} and Felix Nampanya and Ramya Nityanandam and Laurent Pessaint and Maciel Porto and Vaneesha Ali and Dalia Benetiene and Komlan Tevi and Hanne Andersen and Lewis, {Mark G.} and Schmidt, {Aaron G.} and Lauffenburger, {Douglas A.} and Galit Alter and Estes, {Jacob D.} and Hanneke Schuitemaker and Roland Zahn and Barouch, {Dan H.}",

note = "Funding Information: We thank J. van Hoof, M. Mammon, P. Stoffels, D. van Manen, T. Kwaks, K. Bauer, N. Callaham, L. Mistretta, A. Thomas, A. Chandrashekar, L. Peter, L. Maxfield, M. Lifton, E. Borducchi, M. Silva, A. Richardson and C. Caron for generous advice, assistance and reagents. We acknowledge support from the Bill & Melinda Gates Foundation (INV-006131), Janssen Vaccines & Prevention BV, the Ragon Institute of MGH, MIT and Harvard, the Mark and Lisa Schwartz Foundation, the Massachusetts Consortium on Pathogen Readiness and the National Institutes of Health (OD024917, AI129797, AI124377, AI128751, AI126603 to D.H.B.; AI007387 to L.H.T.; AI146779 to A.G.S.; AI135098 to A.J.M.; and OD011092, OD025002 to J.D.E.). This project was funded, in part, by the Department of Health and Human Services Biomedical Advanced Research and Development Authority under contract HHS0100201700018C. We also acknowledge a Fast Grant, Emergent Ventures, Mercatus Center at George Mason University to A.J.M. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = nov,

doi = "10.1038/s41591-020-1070-6",

language = "English (US)",

volume = "26",

pages = "1694--1700",

journal = "Nature medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

number = "11",

}

TY - JOUR

T1 - Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

AU - Tostanoski, Lisa H.

AU - Wegmann, Frank

AU - Martinot, Amanda J.

AU - Loos, Carolin

AU - McMahan, Katherine

AU - Mercado, Noe B.

AU - Yu, Jingyou

AU - Chan, Chi N.

AU - Bondoc, Stephen

AU - Starke, Carly E.

AU - Nekorchuk, Michael

AU - Busman-Sahay, Kathleen

AU - Piedra-Mora, Cesar

AU - Wrijil, Linda M.

AU - Ducat, Sarah

AU - Custers, Jerome

AU - Atyeo, Caroline

AU - Fischinger, Stephanie

AU - Burke, John S.

AU - Feldman, Jared

AU - Hauser, Blake M.

AU - Caradonna, Timothy M.

AU - Bondzie, Esther A.

AU - Dagotto, Gabriel

AU - Gebre, Makda S.

AU - Jacob-Dolan, Catherine

AU - Lin, Zijin

AU - Mahrokhian, Shant H.

AU - Nampanya, Felix

AU - Nityanandam, Ramya

AU - Pessaint, Laurent

AU - Porto, Maciel

AU - Ali, Vaneesha

AU - Benetiene, Dalia

AU - Tevi, Komlan

AU - Andersen, Hanne

AU - Lewis, Mark G.

AU - Schmidt, Aaron G.

AU - Lauffenburger, Douglas A.

AU - Alter, Galit

AU - Estes, Jacob D.

AU - Schuitemaker, Hanneke

AU - Zahn, Roland

AU - Barouch, Dan H.

N1 - Funding Information: We thank J. van Hoof, M. Mammon, P. Stoffels, D. van Manen, T. Kwaks, K. Bauer, N. Callaham, L. Mistretta, A. Thomas, A. Chandrashekar, L. Peter, L. Maxfield, M. Lifton, E. Borducchi, M. Silva, A. Richardson and C. Caron for generous advice, assistance and reagents. We acknowledge support from the Bill & Melinda Gates Foundation (INV-006131), Janssen Vaccines & Prevention BV, the Ragon Institute of MGH, MIT and Harvard, the Mark and Lisa Schwartz Foundation, the Massachusetts Consortium on Pathogen Readiness and the National Institutes of Health (OD024917, AI129797, AI124377, AI128751, AI126603 to D.H.B.; AI007387 to L.H.T.; AI146779 to A.G.S.; AI135098 to A.J.M.; and OD011092, OD025002 to J.D.E.). This project was funded, in part, by the Department of Health and Human Services Biomedical Advanced Research and Development Authority under contract HHS0100201700018C. We also acknowledge a Fast Grant, Emergent Ventures, Mercatus Center at George Mason University to A.J.M. Publisher Copyright: © 2020, The Author(s).

PY - 2020/11

Y1 - 2020/11

N2 - Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death1–4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters5–7 and nonhuman primates8–10 have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates11–13. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.

AB - Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death1–4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters5–7 and nonhuman primates8–10 have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates11–13. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.

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JO - Nature medicine

JF - Nature medicine

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ER -

Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

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