Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques

Kevin R. Bewley; Karen Gooch; Kelly M. Thomas; Stephanie Longet; Nathan Wiblin; Laura Hunter; Kin Chan; Phillip Brown; Rebecca A. Russell; Catherine Ho; Gillian Slack; Holly E. Humphries; Leonie Alden; Lauren Allen; Marilyn Aram; Natalie Baker; Emily Brunt; Rebecca Cobb; Susan Fotheringham; Debbie Harris; Chelsea Kennard; Stephanie Leung; Kathryn Ryan; Howard Tolley; Nadina Wand; Andrew White; Laura Sibley; Charlotte Sarfas; Geoff Pearson; Emma Rayner; Xiaochao Xue; Teresa Lambe; Sue Charlton; Sarah Gilbert; Quentin J. Sattentau; Fergus Gleeson; Yper Hall; Simon Funnell; Sally Sharpe; Francisco J. Salguero; Andrew Gorringe; Miles Carroll

doi:10.1126/sciadv.abg7996

Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques

Kevin R. Bewley, Karen Gooch, Kelly M. Thomas, Stephanie Longet, Nathan Wiblin, Laura Hunter, Kin Chan, Phillip Brown, Rebecca A. Russell, Catherine Ho, Gillian Slack, Holly E. Humphries, Leonie Alden, Lauren Allen, Marilyn Aram, Natalie Baker, Emily Brunt, Rebecca Cobb, Susan Fotheringham, Debbie HarrisChelsea Kennard, Stephanie Leung, Kathryn Ryan, Howard Tolley, Nadina Wand, Andrew White, Laura Sibley, Charlotte Sarfas, Geoff Pearson, Emma Rayner, Xiaochao Xue, Teresa Lambe, Sue Charlton, Sarah Gilbert, Quentin J. Sattentau, Fergus Gleeson, Yper Hall, Simon Funnell, Sally Sharpe, Francisco J. Salguero, Andrew Gorringe^*, Miles Carroll

^*Corresponding author for this work

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

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Abstract

There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines. We have used ferrets and rhesus macaques challenged with SARS-CoV-2 to assess the potential for VED in animals vaccinated with formaldehyde-inactivated SARS-CoV-2 (FIV) formulated with Alhydrogel, compared to a negative control vaccine. We showed no evidence of enhanced disease in ferrets or rhesus macaques given FIV except for mild transient enhanced disease seen 7 days after infection in ferrets. This increased lung pathology was observed at day 7 but was resolved by day 15. We also demonstrate that formaldehyde treatment of SARS-CoV-2 reduces exposure of the spike receptor binding domain providing a mechanistic explanation for suboptimal immunity.

Original language	English
Article number	7996
Number of pages	17
Journal	Science Advances
Volume	7
Issue number	37
DOIs	https://doi.org/10.1126/sciadv.abg7996
Publication status	Published - 10 Sept 2021

Bibliographical note

Funding Information: This work was supported by UKRI Grant MC_PC_19080 and MRC UKRI Grant MC_PC_19055. Viral stock preparation was funded by the Coalition for Epidemic Preparedness Innovations.

Open Access: Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Publisher Copyright: Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Citation: Bewley, Kevin R., et al. "Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques." Science advances 7.37 (2021): eabg7996.

DOI: 10.1126/sciadv.abg7996

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Bewley, K. R., Gooch, K., Thomas, K. M., Longet, S., Wiblin, N., Hunter, L., Chan, K., Brown, P., Russell, R. A., Ho, C., Slack, G., Humphries, H. E., Alden, L., Allen, L., Aram, M., Baker, N., Brunt, E., Cobb, R., Fotheringham, S., ... Carroll, M. (2021). Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques. Science Advances, 7(37), Article 7996. https://doi.org/10.1126/sciadv.abg7996

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title = "Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques",

abstract = "There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines. We have used ferrets and rhesus macaques challenged with SARS-CoV-2 to assess the potential for VED in animals vaccinated with formaldehyde-inactivated SARS-CoV-2 (FIV) formulated with Alhydrogel, compared to a negative control vaccine. We showed no evidence of enhanced disease in ferrets or rhesus macaques given FIV except for mild transient enhanced disease seen 7 days after infection in ferrets. This increased lung pathology was observed at day 7 but was resolved by day 15. We also demonstrate that formaldehyde treatment of SARS-CoV-2 reduces exposure of the spike receptor binding domain providing a mechanistic explanation for suboptimal immunity.",

author = "Bewley, {Kevin R.} and Karen Gooch and Thomas, {Kelly M.} and Stephanie Longet and Nathan Wiblin and Laura Hunter and Kin Chan and Phillip Brown and Russell, {Rebecca A.} and Catherine Ho and Gillian Slack and Humphries, {Holly E.} and Leonie Alden and Lauren Allen and Marilyn Aram and Natalie Baker and Emily Brunt and Rebecca Cobb and Susan Fotheringham and Debbie Harris and Chelsea Kennard and Stephanie Leung and Kathryn Ryan and Howard Tolley and Nadina Wand and Andrew White and Laura Sibley and Charlotte Sarfas and Geoff Pearson and Emma Rayner and Xiaochao Xue and Teresa Lambe and Sue Charlton and Sarah Gilbert and Sattentau, {Quentin J.} and Fergus Gleeson and Yper Hall and Simon Funnell and Sally Sharpe and Salguero, {Francisco J.} and Andrew Gorringe and Miles Carroll",

note = "Funding Information: This work was supported by UKRI Grant MC_PC_19080 and MRC UKRI Grant MC_PC_19055. Viral stock preparation was funded by the Coalition for Epidemic Preparedness Innovations. Open Access: Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Citation: Bewley, Kevin R., et al. {"}Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques.{"} Science advances 7.37 (2021): eabg7996. DOI: 10.1126/sciadv.abg7996",

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month = sep,

day = "10",

doi = "10.1126/sciadv.abg7996",

language = "English",

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Bewley, KR , Gooch, K , Thomas, KM, Longet, S, Wiblin, N, Hunter, L, Chan, K, Brown, P, Russell, RA, Ho, C, Slack, G , Humphries, HE, Alden, L, Allen, L, Aram, M, Baker, N, Brunt, E, Cobb, R, Fotheringham, S, Harris, D, Kennard, C, Leung, S , Ryan, K, Tolley, H, Wand, N, White, A, Sibley, L, Sarfas, C, Pearson, G, Rayner, E, Xue, X, Lambe, T, Charlton, S, Gilbert, S, Sattentau, QJ, Gleeson, F, Hall, Y, Funnell, S , Sharpe, S , Salguero, FJ , Gorringe, A & Carroll, M 2021, 'Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques', Science Advances, vol. 7, no. 37, 7996. https://doi.org/10.1126/sciadv.abg7996

TY - JOUR

T1 - Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques

AU - Bewley, Kevin R.

AU - Gooch, Karen

AU - Thomas, Kelly M.

AU - Longet, Stephanie

AU - Wiblin, Nathan

AU - Hunter, Laura

AU - Chan, Kin

AU - Brown, Phillip

AU - Russell, Rebecca A.

AU - Ho, Catherine

AU - Slack, Gillian

AU - Humphries, Holly E.

AU - Alden, Leonie

AU - Allen, Lauren

AU - Aram, Marilyn

AU - Baker, Natalie

AU - Brunt, Emily

AU - Cobb, Rebecca

AU - Fotheringham, Susan

AU - Harris, Debbie

AU - Kennard, Chelsea

AU - Leung, Stephanie

AU - Ryan, Kathryn

AU - Tolley, Howard

AU - Wand, Nadina

AU - White, Andrew

AU - Sibley, Laura

AU - Sarfas, Charlotte

AU - Pearson, Geoff

AU - Rayner, Emma

AU - Xue, Xiaochao

AU - Lambe, Teresa

AU - Charlton, Sue

AU - Gilbert, Sarah

AU - Sattentau, Quentin J.

AU - Gleeson, Fergus

AU - Hall, Yper

AU - Funnell, Simon

AU - Sharpe, Sally

AU - Salguero, Francisco J.

AU - Gorringe, Andrew

AU - Carroll, Miles

N1 - Funding Information: This work was supported by UKRI Grant MC_PC_19080 and MRC UKRI Grant MC_PC_19055. Viral stock preparation was funded by the Coalition for Epidemic Preparedness Innovations. Open Access: Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Publisher Copyright: Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Citation: Bewley, Kevin R., et al. "Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques." Science advances 7.37 (2021): eabg7996. DOI: 10.1126/sciadv.abg7996

PY - 2021/9/10

Y1 - 2021/9/10

N2 - There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines. We have used ferrets and rhesus macaques challenged with SARS-CoV-2 to assess the potential for VED in animals vaccinated with formaldehyde-inactivated SARS-CoV-2 (FIV) formulated with Alhydrogel, compared to a negative control vaccine. We showed no evidence of enhanced disease in ferrets or rhesus macaques given FIV except for mild transient enhanced disease seen 7 days after infection in ferrets. This increased lung pathology was observed at day 7 but was resolved by day 15. We also demonstrate that formaldehyde treatment of SARS-CoV-2 reduces exposure of the spike receptor binding domain providing a mechanistic explanation for suboptimal immunity.

AB - There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines. We have used ferrets and rhesus macaques challenged with SARS-CoV-2 to assess the potential for VED in animals vaccinated with formaldehyde-inactivated SARS-CoV-2 (FIV) formulated with Alhydrogel, compared to a negative control vaccine. We showed no evidence of enhanced disease in ferrets or rhesus macaques given FIV except for mild transient enhanced disease seen 7 days after infection in ferrets. This increased lung pathology was observed at day 7 but was resolved by day 15. We also demonstrate that formaldehyde treatment of SARS-CoV-2 reduces exposure of the spike receptor binding domain providing a mechanistic explanation for suboptimal immunity.

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U2 - 10.1126/sciadv.abg7996

DO - 10.1126/sciadv.abg7996

M3 - Article

AN - SCOPUS:85114787407

SN - 2375-2548

VL - 7

JO - Science Advances

JF - Science Advances

IS - 37

M1 - 7996

ER -

Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques

Abstract

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