New Results
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
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
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
Aslaa Ahmed
5Viral Diseases Branch, WRAIR, Silver Spring MD 20910, USA
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
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
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
Rita E. Chen
6Department of Medicine, Washington University, St. Louis, MO 63130, USA
7Department of Pathology & Immunology, Washington University, St. Louis, MO 63130, USA
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
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
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
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
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
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
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
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
Clayton Smith
8Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA
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
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
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
Hanne A. Elyard
9Bioqual, Rockville, MD 20850, USA
Anthony Cook
9Bioqual, Rockville, MD 20850, USA
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
Kathryn McGuckin-Wuertz
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
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
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
James B. Case
6Department of Medicine, Washington University, St. Louis, MO 63130, USA
Jeffrey R. Currier
5Viral Diseases Branch, WRAIR, Silver Spring MD 20910, USA
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
Robert J. O’Connell
10WRAIR, Silver Spring MD 20910, USA
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
Manoj S. Nair
15Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
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
Sharon P. Daye
11Center for Infectious Diseases Research, WRAIR, Silver Spring MD 20910, USA
Xiankun Zeng
12Division of Pathology, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA
Erica K. Barkei
13Veterinary Medicine Branch, WRAIR, Silver Spring MD 20910, USA
Hilary M. Staples
14Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio TX 78227, USA
Kendra Alfson
14Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio TX 78227, USA
Ricardo Carrion
14Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio TX 78227, USA
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
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
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
Victoria R. Polonis
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
Linda L. Jagodzinski
4Diagnostics and Countermeasures Branch, WRAIR, Silver Spring MD 20910, USA
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
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
Paul T. Scott
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
Yaoxing Huang
15Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
David D. Ho
15Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
Natalia de Val
8Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA
Michael S. Diamond
6Department of Medicine, Washington University, St. Louis, MO 63130, USA
7Department of Pathology & Immunology, Washington University, St. Louis, MO 63130, USA
Mark G. Lewis
9Bioqual, Rockville, MD 20850, USA
Mangala Rao
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
Gary R. Matyas
3US Military HIV Research Program, WRAIR, Silver Spring MD 20910, USA
Gregory D. Gromowski
5Viral Diseases Branch, WRAIR, Silver Spring MD 20910, USA
Sheila A. Peel
4Diagnostics and Countermeasures Branch, WRAIR, Silver Spring MD 20910, USA
Nelson L. Michael
11Center for Infectious Diseases Research, WRAIR, Silver Spring MD 20910, USA
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
Kayvon Modjarrad
1Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA
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.
Posted March 25, 2021.
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
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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