One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model

Karen Gooch; Trevor R.F. Smith; Francisco Javier Salguero Bodes; Susan Fotheringham; Robert Watson; Michael Dennis; Alastair Handley; Holly Humphries; Stephanie Longet; Thomas Tipton; Charlotte Sarfas; Laura Sibley; Gillian Slack; Emma Rayner; Kathryn Ryan; Katherine Schultheis; Stephanie J. Ramos; Andrew White; Susan Charlton; Sally Sharpe; Fergus Gleeson; Laurent M. Humeau; Yper Hall; Kate E. Broderick; Miles Carroll

doi:10.1016/j.vaccine.2021.06.057

One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model

Karen Gooch, Trevor R.F. Smith, Francisco Javier Salguero Bodes, Susan Fotheringham, Robert Watson, Michael Dennis, Alastair Handley, Holly Humphries, Stephanie Longet, Thomas Tipton, Charlotte Sarfas, Laura Sibley, Gillian Slack, Emma Rayner, Kathryn Ryan, Katherine Schultheis, Stephanie J. Ramos, Andrew White, Susan Charlton, Sally SharpeFergus Gleeson, Laurent M. Humeau, Yper Hall, Kate E. Broderick^*, Miles Carroll

^*Corresponding author for this work

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Abstract

Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of INO4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induced both binding and neutralizing antibodies, along with IFN-gamma-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 x 10(6) pfu) via the intranasal and intratracheal routes we observed significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 was associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provided no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen.

Original language	English
Pages (from-to)	4885-4894
Journal	Vaccine
Volume	39
Issue number	34
Early online date	23 Jun 2021
DOIs	https://doi.org/10.1016/j.vaccine.2021.06.057
Publication status	Published - 9 Aug 2021

Bibliographical note

Funding Information: The studies described in this manuscript were funded by a grant from the Coalition for Epidemic Preparedness Innovations (CEPI). The authors would like to thank Amy Shurtleff for her expert advice throughout this study. We would also like to thank the David Weiner laboratory at the Wistar Institute for their valuable support of the INO-4800 vaccine program. We would like to thank Maria Yang and the Inovio plasmid production team for generating the DNA constructs and formulation, Matthew Coultas and the Inovio logistics team for overseeing shipment of the biologics and drug delivery equipment. Thank you to Lauren Allen, Emily Brunt, Breeze E Cavell, Rebecca Cobb, Konstantinos Gkolfinos, Kerry J Godwin, Jade Gouriet, Richard Hesp, Charlotte Hind, Catherine M. K. Ho, Stephanie Leung, Jennifer Logue, Vanessa Lucas, Adam Mabbutt, Alexandra Morrison, Jemma Patterson, Elizabeth J. Penn, Stephen Thomas, Nadina Wand for assistance with sample processing and analysis, Laura Hunter and Chelsea Kennard for histology analysis and Debbie Harris, Nathan Wiblin and all Biological Investigations Group staff for animal husbandry and assistance with in vivo procedures.

Open Access: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Publisher Copyright: Crown Copyright © 2021 Published by Elsevier Ltd.

Citation: Karen E. Gooch, Trevor R.F. Smith, Francisco J. Salguero, Susan A. Fotheringham, Robert J. Watson, Mike J. Dennis, Alastair Handley, Holly E. Humphries, Stephanie Longet, Tom Tipton, Charlotte Sarfas, Laura Sibley, Gillian S. Slack, Emma Rayner, Kathryn A. Ryan, Katherine Schultheis, Stephanie J. Ramos, Andrew White, Sue Charlton, Sally A. Sharpe, Fergus Gleeson, Laurent M. Humeau, Yper Hall, Kate E. Broderick, Miles W. Carroll, One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model, Vaccine, Volume 39, Issue 34, 2021, Pages 4885-4894, ISSN 0264-410X.

DOI: https://doi.org/10.1016/j.vaccine.2021.06.057.

Keywords

COVID-19
DNA vaccine
Nonhuman Primate Virus Challenge
SARS-CoV-2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Gooch2021OneOrTwoDoseRegimenOfTheSARS-CoV-2SyntheticVaccineFinal published version, 1.24 MBLicence: CC BY-NC-ND

Cite this

Gooch, K., Smith, T. R. F., Salguero Bodes, F. J., Fotheringham, S., Watson, R., Dennis, M., Handley, A., Humphries, H., Longet, S., Tipton, T., Sarfas, C., Sibley, L., Slack, G., Rayner, E., Ryan, K., Schultheis, K., Ramos, S. J., White, A., Charlton, S., ... Carroll, M. (2021). One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model. Vaccine, 39(34), 4885-4894. https://doi.org/10.1016/j.vaccine.2021.06.057

@article{76703cbdef194bacbfb7600932e523cc,

title = "One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model",

abstract = "Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of INO4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induced both binding and neutralizing antibodies, along with IFN-gamma-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 x 10(6) pfu) via the intranasal and intratracheal routes we observed significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 was associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provided no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen. ",

keywords = "COVID-19, DNA vaccine, Nonhuman Primate Virus Challenge, SARS-CoV-2",

author = "Karen Gooch and Smith, {Trevor R.F.} and {Salguero Bodes}, {Francisco Javier} and Susan Fotheringham and Robert Watson and Michael Dennis and Alastair Handley and Holly Humphries and Stephanie Longet and Thomas Tipton and Charlotte Sarfas and Laura Sibley and Gillian Slack and Emma Rayner and Kathryn Ryan and Katherine Schultheis and Ramos, {Stephanie J.} and Andrew White and Susan Charlton and Sally Sharpe and Fergus Gleeson and Humeau, {Laurent M.} and Yper Hall and Broderick, {Kate E.} and Miles Carroll",

note = "Funding Information: The studies described in this manuscript were funded by a grant from the Coalition for Epidemic Preparedness Innovations (CEPI). The authors would like to thank Amy Shurtleff for her expert advice throughout this study. We would also like to thank the David Weiner laboratory at the Wistar Institute for their valuable support of the INO-4800 vaccine program. We would like to thank Maria Yang and the Inovio plasmid production team for generating the DNA constructs and formulation, Matthew Coultas and the Inovio logistics team for overseeing shipment of the biologics and drug delivery equipment. Thank you to Lauren Allen, Emily Brunt, Breeze E Cavell, Rebecca Cobb, Konstantinos Gkolfinos, Kerry J Godwin, Jade Gouriet, Richard Hesp, Charlotte Hind, Catherine M. K. Ho, Stephanie Leung, Jennifer Logue, Vanessa Lucas, Adam Mabbutt, Alexandra Morrison, Jemma Patterson, Elizabeth J. Penn, Stephen Thomas, Nadina Wand for assistance with sample processing and analysis, Laura Hunter and Chelsea Kennard for histology analysis and Debbie Harris, Nathan Wiblin and all Biological Investigations Group staff for animal husbandry and assistance with in vivo procedures. Open Access: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Publisher Copyright: Crown Copyright {\textcopyright} 2021 Published by Elsevier Ltd. Citation: Karen E. Gooch, Trevor R.F. Smith, Francisco J. Salguero, Susan A. Fotheringham, Robert J. Watson, Mike J. Dennis, Alastair Handley, Holly E. Humphries, Stephanie Longet, Tom Tipton, Charlotte Sarfas, Laura Sibley, Gillian S. Slack, Emma Rayner, Kathryn A. Ryan, Katherine Schultheis, Stephanie J. Ramos, Andrew White, Sue Charlton, Sally A. Sharpe, Fergus Gleeson, Laurent M. Humeau, Yper Hall, Kate E. Broderick, Miles W. Carroll, One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model, Vaccine, Volume 39, Issue 34, 2021, Pages 4885-4894, ISSN 0264-410X. DOI: https://doi.org/10.1016/j.vaccine.2021.06.057.",

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Gooch, K, Smith, TRF, Salguero Bodes, FJ , Fotheringham, S , Watson, R , Dennis, M, Handley, A, Humphries, H, Longet, S, Tipton, T, Sarfas, C, Sibley, L, Slack, G , Rayner, E , Ryan, K, Schultheis, K, Ramos, SJ, White, A , Charlton, S , Sharpe, S, Gleeson, F, Humeau, LM, Hall, Y, Broderick, KE & Carroll, M 2021, 'One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model', Vaccine, vol. 39, no. 34, pp. 4885-4894. https://doi.org/10.1016/j.vaccine.2021.06.057

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T1 - One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model

AU - Gooch, Karen

AU - Smith, Trevor R.F.

AU - Salguero Bodes, Francisco Javier

AU - Fotheringham, Susan

AU - Watson, Robert

AU - Dennis, Michael

AU - Handley, Alastair

AU - Humphries, Holly

AU - Longet, Stephanie

AU - Tipton, Thomas

AU - Sarfas, Charlotte

AU - Sibley, Laura

AU - Slack, Gillian

AU - Rayner, Emma

AU - Ryan, Kathryn

AU - Schultheis, Katherine

AU - Ramos, Stephanie J.

AU - White, Andrew

AU - Charlton, Susan

AU - Sharpe, Sally

AU - Gleeson, Fergus

AU - Humeau, Laurent M.

AU - Hall, Yper

AU - Broderick, Kate E.

AU - Carroll, Miles

N1 - Funding Information: The studies described in this manuscript were funded by a grant from the Coalition for Epidemic Preparedness Innovations (CEPI). The authors would like to thank Amy Shurtleff for her expert advice throughout this study. We would also like to thank the David Weiner laboratory at the Wistar Institute for their valuable support of the INO-4800 vaccine program. We would like to thank Maria Yang and the Inovio plasmid production team for generating the DNA constructs and formulation, Matthew Coultas and the Inovio logistics team for overseeing shipment of the biologics and drug delivery equipment. Thank you to Lauren Allen, Emily Brunt, Breeze E Cavell, Rebecca Cobb, Konstantinos Gkolfinos, Kerry J Godwin, Jade Gouriet, Richard Hesp, Charlotte Hind, Catherine M. K. Ho, Stephanie Leung, Jennifer Logue, Vanessa Lucas, Adam Mabbutt, Alexandra Morrison, Jemma Patterson, Elizabeth J. Penn, Stephen Thomas, Nadina Wand for assistance with sample processing and analysis, Laura Hunter and Chelsea Kennard for histology analysis and Debbie Harris, Nathan Wiblin and all Biological Investigations Group staff for animal husbandry and assistance with in vivo procedures. Open Access: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Publisher Copyright: Crown Copyright © 2021 Published by Elsevier Ltd. Citation: Karen E. Gooch, Trevor R.F. Smith, Francisco J. Salguero, Susan A. Fotheringham, Robert J. Watson, Mike J. Dennis, Alastair Handley, Holly E. Humphries, Stephanie Longet, Tom Tipton, Charlotte Sarfas, Laura Sibley, Gillian S. Slack, Emma Rayner, Kathryn A. Ryan, Katherine Schultheis, Stephanie J. Ramos, Andrew White, Sue Charlton, Sally A. Sharpe, Fergus Gleeson, Laurent M. Humeau, Yper Hall, Kate E. Broderick, Miles W. Carroll, One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model, Vaccine, Volume 39, Issue 34, 2021, Pages 4885-4894, ISSN 0264-410X. DOI: https://doi.org/10.1016/j.vaccine.2021.06.057.

PY - 2021/8/9

Y1 - 2021/8/9

N2 - Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of INO4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induced both binding and neutralizing antibodies, along with IFN-gamma-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 x 10(6) pfu) via the intranasal and intratracheal routes we observed significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 was associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provided no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen.

AB - Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of INO4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induced both binding and neutralizing antibodies, along with IFN-gamma-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 x 10(6) pfu) via the intranasal and intratracheal routes we observed significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 was associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provided no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen.

KW - COVID-19

KW - DNA vaccine

KW - Nonhuman Primate Virus Challenge

KW - SARS-CoV-2

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M3 - Article

AN - SCOPUS:85110466252

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ER -

One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model

Abstract

Bibliographical note

Keywords

UN SDGs

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