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Efficacy of a Broadly Neutralizing SARS-CoV-2 Ferritin Nanoparticle Vaccine in Nonhuman Primates

Michael G. Joyce, Hannah A. D. King, Ines Elakhal Naouar, Aslaa Ahmed, Kristina K. Peachman, Camila Macedo Cincotta, Caroline Subra, Rita E. Chen, Paul V. Thomas, Wei-Hung Chen, Rajeshwer S. Sankhala, Agnes Hajduczki, Elizabeth J. Martinez, Caroline E. Peterson, William C. Chang, Misook Choe, Clayton Smith, Parker J. Lee, Jarrett A. Headley, Mekdi G. Taddese, Hanne A. Elyard, Anthony Cook, Alexander Anderson, Kathryn McGuckin-Wuertz, Ming Dong, Isabella Swafford, James B. Case, Jeffrey R. Currier, Kerri G. Lal, Robert J. O’Connell, Sebastian Molnar, Manoj S. Nair, Vincent Dussupt, Sharon P. Daye, Xiankun Zeng, Erica K. Barkei, Hilary M. Staples, Kendra Alfson, Ricardo Carrion, Shelly J. Krebs, Dominic Paquin-Proulx, Nicos Karasavva, Victoria R. Polonis, Linda L. Jagodzinski, Mihret F. Amare, Sandhya Vasan, Paul T. Scott, Yaoxing Huang, David D. Ho, Natalia de Val, Michael S. Diamond, Mark G. Lewis, Mangala Rao, Gary R. Matyas, Gregory D. Gromowski, Sheila A. Peel, Nelson L. Michael, Diane L. Bolton, Kayvon Modjarrad
doi: https://doi.org/10.1101/2021.03.24.436523
Michael G. Joyce
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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  • For correspondence: kayvon.modjarrad.civ@mail.mil gjoyce@eidresearch.org
Hannah A. D. King
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Ines Elakhal Naouar
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
4Diagnostics and Countermeasures Branch, WRAIR, Silver Spring MD 20910, USA
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Aslaa Ahmed
5Viral Diseases Branch, WRAIR, Silver Spring MD 20910, USA
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Kristina K. Peachman
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
4Diagnostics and Countermeasures Branch, WRAIR, Silver Spring MD 20910, USA
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Camila Macedo Cincotta
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
4Diagnostics and Countermeasures Branch, WRAIR, Silver Spring MD 20910, USA
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Caroline Subra
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Rita E. Chen
6Department of Medicine, Washington University, St. Louis, MO 63130, USA
7Department of Pathology & Immunology, Washington University, St. Louis, MO 63130, USA
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Paul V. Thomas
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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Wei-Hung Chen
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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Rajeshwer S. Sankhala
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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Agnes Hajduczki
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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Elizabeth J. Martinez
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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Caroline E. Peterson
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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William C. Chang
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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Misook Choe
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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Clayton Smith
8Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA
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Parker J. Lee
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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Jarrett A. Headley
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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Mekdi G. Taddese
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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Hanne A. Elyard
9Bioqual, Rockville, MD 20850, USA
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Anthony Cook
9Bioqual, Rockville, MD 20850, USA
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Alexander Anderson
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Kathryn McGuckin-Wuertz
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Ming Dong
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Isabella Swafford
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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James B. Case
6Department of Medicine, Washington University, St. Louis, MO 63130, USA
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Jeffrey R. Currier
5Viral Diseases Branch, WRAIR, Silver Spring MD 20910, USA
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Kerri G. Lal
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Robert J. O’Connell
10WRAIR, Silver Spring MD 20910, USA
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Sebastian Molnar
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Manoj S. Nair
15Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Vincent Dussupt
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Sharon P. Daye
11Center for Infectious Diseases Research, WRAIR, Silver Spring MD 20910, USA
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Xiankun Zeng
12Division of Pathology, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA
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Erica K. Barkei
13Veterinary Medicine Branch, WRAIR, Silver Spring MD 20910, USA
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Hilary M. Staples
14Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio TX 78227, USA
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Kendra Alfson
14Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio TX 78227, USA
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Ricardo Carrion
14Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio TX 78227, USA
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Shelly J. Krebs
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Dominic Paquin-Proulx
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Nicos Karasavva
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
4Diagnostics and Countermeasures Branch, WRAIR, Silver Spring MD 20910, USA
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Victoria R. Polonis
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Linda L. Jagodzinski
4Diagnostics and Countermeasures Branch, WRAIR, Silver Spring MD 20910, USA
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Mihret F. Amare
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
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Sandhya Vasan
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Paul T. Scott
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
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Yaoxing Huang
15Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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David D. Ho
15Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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Natalia de Val
8Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA
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Michael S. Diamond
6Department of Medicine, Washington University, St. Louis, MO 63130, USA
7Department of Pathology & Immunology, Washington University, St. Louis, MO 63130, USA
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Mark G. Lewis
9Bioqual, Rockville, MD 20850, USA
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Mangala Rao
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Gary R. Matyas
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Gregory D. Gromowski
5Viral Diseases Branch, WRAIR, Silver Spring MD 20910, USA
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Sheila A. Peel
4Diagnostics and Countermeasures Branch, WRAIR, Silver Spring MD 20910, USA
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Nelson L. Michael
11Center for Infectious Diseases Research, WRAIR, Silver Spring MD 20910, USA
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Diane L. Bolton
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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Kayvon Modjarrad
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
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  • For correspondence: kayvon.modjarrad.civ@mail.mil gjoyce@eidresearch.org
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Abstract

The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine in nonhuman primates (NHPs). High-dose (50 µg) SpFN vaccine, given twice within a 28 day interval, induced a Th1-biased CD4 T cell helper response and a peak neutralizing antibody geometric mean titer of 52,773 against wild-type virus, with activity against SARS-CoV-1 and minimal decrement against variants of concern. Vaccinated animals mounted an anamnestic response upon high-dose SARS-CoV-2 respiratory challenge that translated into rapid elimination of replicating virus in their upper and lower airways and lung parenchyma. SpFN’s potent and broad immunogenicity profile and resulting efficacy in NHPs supports its utility as a candidate platform for SARS-like betacoronaviruses.

One-Sentence Summary A SARS-CoV-2 Spike protein ferritin nanoparticle vaccine, co-formulated with a liposomal adjuvant, elicits broad neutralizing antibody responses that exceed those observed for other major vaccines and rapidly protects against respiratory infection and disease in the upper and lower airways and lung tissue of nonhuman primates.

Competing Interest Statement

M. Gordon Joyce and Kayvon Modjarrad are primary co-inventors on pending patents for material presented in this manuscript.

Copyright 
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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Efficacy of a Broadly Neutralizing SARS-CoV-2 Ferritin Nanoparticle Vaccine in Nonhuman Primates
Michael G. Joyce, Hannah A. D. King, Ines Elakhal Naouar, Aslaa Ahmed, Kristina K. Peachman, Camila Macedo Cincotta, Caroline Subra, Rita E. Chen, Paul V. Thomas, Wei-Hung Chen, Rajeshwer S. Sankhala, Agnes Hajduczki, Elizabeth J. Martinez, Caroline E. Peterson, William C. Chang, Misook Choe, Clayton Smith, Parker J. Lee, Jarrett A. Headley, Mekdi G. Taddese, Hanne A. Elyard, Anthony Cook, Alexander Anderson, Kathryn McGuckin-Wuertz, Ming Dong, Isabella Swafford, James B. Case, Jeffrey R. Currier, Kerri G. Lal, Robert J. O’Connell, Sebastian Molnar, Manoj S. Nair, Vincent Dussupt, Sharon P. Daye, Xiankun Zeng, Erica K. Barkei, Hilary M. Staples, Kendra Alfson, Ricardo Carrion, Shelly J. Krebs, Dominic Paquin-Proulx, Nicos Karasavva, Victoria R. Polonis, Linda L. Jagodzinski, Mihret F. Amare, Sandhya Vasan, Paul T. Scott, Yaoxing Huang, David D. Ho, Natalia de Val, Michael S. Diamond, Mark G. Lewis, Mangala Rao, Gary R. Matyas, Gregory D. Gromowski, Sheila A. Peel, Nelson L. Michael, Diane L. Bolton, Kayvon Modjarrad
bioRxiv 2021.03.24.436523; doi: https://doi.org/10.1101/2021.03.24.436523
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Efficacy of a Broadly Neutralizing SARS-CoV-2 Ferritin Nanoparticle Vaccine in Nonhuman Primates
Michael G. Joyce, Hannah A. D. King, Ines Elakhal Naouar, Aslaa Ahmed, Kristina K. Peachman, Camila Macedo Cincotta, Caroline Subra, Rita E. Chen, Paul V. Thomas, Wei-Hung Chen, Rajeshwer S. Sankhala, Agnes Hajduczki, Elizabeth J. Martinez, Caroline E. Peterson, William C. Chang, Misook Choe, Clayton Smith, Parker J. Lee, Jarrett A. Headley, Mekdi G. Taddese, Hanne A. Elyard, Anthony Cook, Alexander Anderson, Kathryn McGuckin-Wuertz, Ming Dong, Isabella Swafford, James B. Case, Jeffrey R. Currier, Kerri G. Lal, Robert J. O’Connell, Sebastian Molnar, Manoj S. Nair, Vincent Dussupt, Sharon P. Daye, Xiankun Zeng, Erica K. Barkei, Hilary M. Staples, Kendra Alfson, Ricardo Carrion, Shelly J. Krebs, Dominic Paquin-Proulx, Nicos Karasavva, Victoria R. Polonis, Linda L. Jagodzinski, Mihret F. Amare, Sandhya Vasan, Paul T. Scott, Yaoxing Huang, David D. Ho, Natalia de Val, Michael S. Diamond, Mark G. Lewis, Mangala Rao, Gary R. Matyas, Gregory D. Gromowski, Sheila A. Peel, Nelson L. Michael, Diane L. Bolton, Kayvon Modjarrad
bioRxiv 2021.03.24.436523; doi: https://doi.org/10.1101/2021.03.24.436523

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