ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models

Teresa Lambe; Alexandra J. Spencer; Kelly Thomas; Karen Gooch; Stephen Thomas; Andrew White; Holly Humphries; Daniel Wright; Sandra Belij-Rammerstorfer; Nazia Thakur; Carina Conceicao; Robert Watson; Leonie Alden; Lauren Allen; Marilyn Aram; Kevin Bewley; Emily Brunt; Phillip Brown; Breeze Cavell; Rebecca Cobb; Susan Fotheringham; Ciaran Gilbride; Deborah Harris; Catherine M.K. Ho; Laura Hunter; Chelsea L. Kennard; Stephanie Leung; Vanessa Lucas; Didier Ngabo; Kathryn Ryan; Hannah Sharpe; Charlotte Sarfas; Laura Sibley; Gillian Slack; Marta Ulaszewska; Nadina Wand; Nathan Wiblin; Fergus V. Gleeson; Dalan Bailey; Sally Sharpe; Susan Charlton; Francisco Javier Salguero Bodes; Miles Carroll; Sarah C. Gilbert

doi:10.1038/s42003-021-02443-0

ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models

Teresa Lambe, Alexandra J. Spencer, Kelly Thomas, Karen Gooch, Stephen Thomas, Andrew White, Holly Humphries, Daniel Wright, Sandra Belij-Rammerstorfer, Nazia Thakur, Carina Conceicao, Robert Watson, Leonie Alden, Lauren Allen, Marilyn Aram, Kevin Bewley, Emily Brunt, Phillip Brown, Breeze Cavell, Rebecca CobbSusan Fotheringham, Ciaran Gilbride, Deborah Harris, Catherine M.K. Ho, Laura Hunter, Chelsea L. Kennard, Stephanie Leung, Vanessa Lucas, Didier Ngabo, Kathryn Ryan, Hannah Sharpe, Charlotte Sarfas, Laura Sibley, Gillian Slack, Marta Ulaszewska, Nadina Wand, Nathan Wiblin, Fergus V. Gleeson, Dalan Bailey, Sally Sharpe, Susan Charlton, Francisco Javier Salguero Bodes, Miles Carroll, Sarah C. Gilbert^*

^*Corresponding author for this work

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Abstract

Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.

Original language	English
Article number	915
Journal	Communications Biology
Volume	4
DOIs	https://doi.org/10.1038/s42003-021-02443-0
Publication status	Published - 26 Jul 2021

Bibliographical note

Funding Information: SCG is co-founder and board member of Vaccitech (collaborators in the early development of this vaccine candidate) and named as an inventor on a patent covering the use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine. TL is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and consultant to Vaccitech. All other authors had no competing interests.

Open Access:This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Publisher Copyright: © The Author(s) 2021

Citation: Lambe, T., Spencer, A.J., Thomas, K.M. et al. ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models. Commun Biol 4, 915 (2021).

DOI: https://doi.org/10.1038/s42003-021-02443-0

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Lambe, T., Spencer, A. J., Thomas, K., Gooch, K., Thomas, S., White, A., Humphries, H., Wright, D., Belij-Rammerstorfer, S., Thakur, N., Conceicao, C., Watson, R., Alden, L., Allen, L., Aram, M., Bewley, K., Brunt, E., Brown, P., Cavell, B., ... Gilbert, S. C. (2021). ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models. Communications Biology, 4, Article 915. https://doi.org/10.1038/s42003-021-02443-0

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title = "ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models",

abstract = "Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.",

author = "Teresa Lambe and Spencer, {Alexandra J.} and Kelly Thomas and Karen Gooch and Stephen Thomas and Andrew White and Holly Humphries and Daniel Wright and Sandra Belij-Rammerstorfer and Nazia Thakur and Carina Conceicao and Robert Watson and Leonie Alden and Lauren Allen and Marilyn Aram and Kevin Bewley and Emily Brunt and Phillip Brown and Breeze Cavell and Rebecca Cobb and Susan Fotheringham and Ciaran Gilbride and Deborah Harris and Ho, {Catherine M.K.} and Laura Hunter and Kennard, {Chelsea L.} and Stephanie Leung and Vanessa Lucas and Didier Ngabo and Kathryn Ryan and Hannah Sharpe and Charlotte Sarfas and Laura Sibley and Gillian Slack and Marta Ulaszewska and Nadina Wand and Nathan Wiblin and Gleeson, {Fergus V.} and Dalan Bailey and Sally Sharpe and Susan Charlton and {Salguero Bodes}, {Francisco Javier} and Miles Carroll and Gilbert, {Sarah C.}",

note = "Funding Information: SCG is co-founder and board member of Vaccitech (collaborators in the early development of this vaccine candidate) and named as an inventor on a patent covering the use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine. TL is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and consultant to Vaccitech. All other authors had no competing interests. Open Access:This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article{\textquoteright}s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article{\textquoteright}s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Publisher Copyright: {\textcopyright} The Author(s) 2021 Citation: Lambe, T., Spencer, A.J., Thomas, K.M. et al. ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models. Commun Biol 4, 915 (2021). DOI: https://doi.org/10.1038/s42003-021-02443-0",

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doi = "10.1038/s42003-021-02443-0",

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Lambe, T, Spencer, AJ, Thomas, K , Gooch, K , Thomas, S , White, A , Humphries, H, Wright, D, Belij-Rammerstorfer, S, Thakur, N, Conceicao, C, Watson, R, Alden, L, Allen, L, Aram, M, Bewley, K, Brunt, E, Brown, P , Cavell, B, Cobb, R, Fotheringham, S, Gilbride, C, Harris, D, Ho, CMK, Hunter, L, Kennard, CL, Leung, S, Lucas, V, Ngabo, D , Ryan, K, Sharpe, H, Sarfas, C, Sibley, L, Slack, G, Ulaszewska, M, Wand, N, Wiblin, N, Gleeson, FV, Bailey, D, Sharpe, S , Charlton, S , Salguero Bodes, FJ, Carroll, M & Gilbert, SC 2021, 'ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models', Communications Biology, vol. 4, 915. https://doi.org/10.1038/s42003-021-02443-0

TY - JOUR

T1 - ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models

AU - Lambe, Teresa

AU - Spencer, Alexandra J.

AU - Thomas, Kelly

AU - Gooch, Karen

AU - Thomas, Stephen

AU - White, Andrew

AU - Humphries, Holly

AU - Wright, Daniel

AU - Belij-Rammerstorfer, Sandra

AU - Thakur, Nazia

AU - Conceicao, Carina

AU - Watson, Robert

AU - Alden, Leonie

AU - Allen, Lauren

AU - Aram, Marilyn

AU - Bewley, Kevin

AU - Brunt, Emily

AU - Brown, Phillip

AU - Cavell, Breeze

AU - Cobb, Rebecca

AU - Fotheringham, Susan

AU - Gilbride, Ciaran

AU - Harris, Deborah

AU - Ho, Catherine M.K.

AU - Hunter, Laura

AU - Kennard, Chelsea L.

AU - Leung, Stephanie

AU - Lucas, Vanessa

AU - Ngabo, Didier

AU - Ryan, Kathryn

AU - Sharpe, Hannah

AU - Sarfas, Charlotte

AU - Sibley, Laura

AU - Slack, Gillian

AU - Ulaszewska, Marta

AU - Wand, Nadina

AU - Wiblin, Nathan

AU - Gleeson, Fergus V.

AU - Bailey, Dalan

AU - Sharpe, Sally

AU - Charlton, Susan

AU - Salguero Bodes, Francisco Javier

AU - Carroll, Miles

AU - Gilbert, Sarah C.

N1 - Funding Information: SCG is co-founder and board member of Vaccitech (collaborators in the early development of this vaccine candidate) and named as an inventor on a patent covering the use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine. TL is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and consultant to Vaccitech. All other authors had no competing interests. Open Access:This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Publisher Copyright: © The Author(s) 2021 Citation: Lambe, T., Spencer, A.J., Thomas, K.M. et al. ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models. Commun Biol 4, 915 (2021). DOI: https://doi.org/10.1038/s42003-021-02443-0

PY - 2021/7/26

Y1 - 2021/7/26

N2 - Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.

AB - Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.

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ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models

Abstract

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