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Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model

Ami Patel, Jewell Walters, Emma L. Reuschel, Katherine Schultheis, Elizabeth Parzych, Ebony N. Gary, Igor Maricic, Mansi Purwar, Zeena Eblimit, Susanne N. Walker, Diana Guimet, Pratik Bhojnagarwala, Arthur Doan, Ziyang Xu, Dustin Elwood, Sophia M. Reeder, Laurent Pessaint, Kevin Y. Kim, Anthony Cook, Neethu Chokkalingam, Brad Finneyfrock, Edgar Tello-Ruiz, Alan Dodson, Jihae Choi, Alison Generotti, John Harrison, Nicholas J. Tursi, Viviane M. Andrade, Yaya Dia, Faraz I. Zaidi, Hanne Andersen, Mark G. Lewis, Kar Muthumani, J Joseph Kim, Daniel W. Kulp, Laurent M. Humeau, Stephanie Ramos, Trevor R.F. Smith, David B. Weiner, Kate E. Broderick
doi: https://doi.org/10.1101/2020.07.28.225649
Ami Patel
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Jewell Walters
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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Emma L. Reuschel
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Katherine Schultheis
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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Elizabeth Parzych
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Ebony N. Gary
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Igor Maricic
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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Mansi Purwar
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Zeena Eblimit
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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Susanne N. Walker
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Diana Guimet
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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Pratik Bhojnagarwala
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Arthur Doan
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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Ziyang Xu
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Dustin Elwood
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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Sophia M. Reeder
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Laurent Pessaint
3Bioqual, Rockville, MD 20852
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Kevin Y. Kim
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Anthony Cook
3Bioqual, Rockville, MD 20852
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Neethu Chokkalingam
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Brad Finneyfrock
3Bioqual, Rockville, MD 20852
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Edgar Tello-Ruiz
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Alan Dodson
3Bioqual, Rockville, MD 20852
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Jihae Choi
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Alison Generotti
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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John Harrison
3Bioqual, Rockville, MD 20852
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Nicholas J. Tursi
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Viviane M. Andrade
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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Yaya Dia
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Faraz I. Zaidi
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Hanne Andersen
3Bioqual, Rockville, MD 20852
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Mark G. Lewis
3Bioqual, Rockville, MD 20852
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Kar Muthumani
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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J Joseph Kim
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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Daniel W. Kulp
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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Laurent M. Humeau
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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Stephanie Ramos
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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Trevor R.F. Smith
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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David B. Weiner
1Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
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  • For correspondence: kate.brodrick@inovio.com
Kate E. Broderick
2Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
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  • For correspondence: kate.brodrick@inovio.com
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Summary

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health, social, and economic infrastructures. Here, we assess immunogenicity and anamnestic protective efficacy in rhesus macaques of the intradermal (ID)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800. INO-4800 is an ID-delivered DNA vaccine currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and neutralizing antibody responses against both the D614 and G614 SARS-CoV-2 spike proteins. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T and B cell responses. These responses were associated with lower viral loads in the lung and with faster nasal clearance of virus. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system which are likely important for providing durable protection against COVID-19 disease.

Competing Interest Statement

A.P., E.R., E.P., E.N.G., M.P., S.N.W., P.B., Z.X., S.R., K.Y.K., N.C., E.T-R., J.C., N.J.T., K.M., D.K.W., declare no competing interests. J.W., K.S., I.M., Z.E., D.G., A.D., D.E., A.G., V.M.A., J.J.K., L.M.H., S.R., T.R.F.S., K.E.B. are employees of Inovio Pharmaceuticals and as such receive salary and benefits, including ownership of stock and stock options, from the company. D.B.W. discloses the following paid associations with commercial partners: GeneOne (Consultant), Geneos (Advisory Board), Astrazeneca (Advisory Board, Speaker), Inovio (BOD, SRA, Stock), Pfizer (Speaker), Merck (Speaker), Sanofi (Advisory Board), BBI (Advisory Board).

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 29, 2020.
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Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model
Ami Patel, Jewell Walters, Emma L. Reuschel, Katherine Schultheis, Elizabeth Parzych, Ebony N. Gary, Igor Maricic, Mansi Purwar, Zeena Eblimit, Susanne N. Walker, Diana Guimet, Pratik Bhojnagarwala, Arthur Doan, Ziyang Xu, Dustin Elwood, Sophia M. Reeder, Laurent Pessaint, Kevin Y. Kim, Anthony Cook, Neethu Chokkalingam, Brad Finneyfrock, Edgar Tello-Ruiz, Alan Dodson, Jihae Choi, Alison Generotti, John Harrison, Nicholas J. Tursi, Viviane M. Andrade, Yaya Dia, Faraz I. Zaidi, Hanne Andersen, Mark G. Lewis, Kar Muthumani, J Joseph Kim, Daniel W. Kulp, Laurent M. Humeau, Stephanie Ramos, Trevor R.F. Smith, David B. Weiner, Kate E. Broderick
bioRxiv 2020.07.28.225649; doi: https://doi.org/10.1101/2020.07.28.225649
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Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model
Ami Patel, Jewell Walters, Emma L. Reuschel, Katherine Schultheis, Elizabeth Parzych, Ebony N. Gary, Igor Maricic, Mansi Purwar, Zeena Eblimit, Susanne N. Walker, Diana Guimet, Pratik Bhojnagarwala, Arthur Doan, Ziyang Xu, Dustin Elwood, Sophia M. Reeder, Laurent Pessaint, Kevin Y. Kim, Anthony Cook, Neethu Chokkalingam, Brad Finneyfrock, Edgar Tello-Ruiz, Alan Dodson, Jihae Choi, Alison Generotti, John Harrison, Nicholas J. Tursi, Viviane M. Andrade, Yaya Dia, Faraz I. Zaidi, Hanne Andersen, Mark G. Lewis, Kar Muthumani, J Joseph Kim, Daniel W. Kulp, Laurent M. Humeau, Stephanie Ramos, Trevor R.F. Smith, David B. Weiner, Kate E. Broderick
bioRxiv 2020.07.28.225649; doi: https://doi.org/10.1101/2020.07.28.225649

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