Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques

Rajeshwer S. Sankhala, Kerri G. Lal, Jaime L. Jensen, Vincent Dussupt, Letzibeth Mendez-Rivera, Hongjun Bai, Lindsay Wieczorek, Sandra V. Mayer, Michelle Zemil, Danielle A. Wagner, Samantha M. Townsley, Agnes Hajduczki, William C. Chang, Wei-Hung Chen, Gina C. Donofrio, Ningbo Jian, Hannah A. D. King, Cynthia G. Lorang, Elizabeth J. Martinez, Phyllis A. Rees, Caroline E. Peterson, Fabian Schmidt, Tricia J. Hart, Debra K. Duso, Lawrence W. Kummer, Sean P. Casey, Jazmean K. Williams, Shruthi Kannan, Bonnie M. Slike, Lauren Smith, Isabella Swafford, Paul V. Thomas, Ursula Tran, Jeffrey R. Currier, Diane L. Bolton, Edgar Davidson, Benjamin J. Doranz, Theodora Hatziioannou, Paul D. Bieniasz, Dominic Paquin-Proulx, William W. Reiley, Morgane Rolland, Nancy J. Sullivan, Sandhya Vasan, Natalie D. Collins, Kayvon Modjarrad, Gregory D. Gromowski, Victoria R. Polonis, Nelson L. Michael, Shelly J. Krebs () and M. Gordon Joyce ()
Additional contact information
Rajeshwer S. Sankhala: Walter Reed Army Institute of Research
Kerri G. Lal: Walter Reed Army Institute of Research
Jaime L. Jensen: Walter Reed Army Institute of Research
Vincent Dussupt: Walter Reed Army Institute of Research
Letzibeth Mendez-Rivera: Henry M. Jackson Foundation for the Advancement of Military Medicine
Hongjun Bai: Walter Reed Army Institute of Research
Lindsay Wieczorek: Henry M. Jackson Foundation for the Advancement of Military Medicine
Sandra V. Mayer: Walter Reed Army Institute of Research
Michelle Zemil: Henry M. Jackson Foundation for the Advancement of Military Medicine
Danielle A. Wagner: National Institutes of Health
Samantha M. Townsley: Henry M. Jackson Foundation for the Advancement of Military Medicine
Agnes Hajduczki: Walter Reed Army Institute of Research
William C. Chang: Walter Reed Army Institute of Research
Wei-Hung Chen: Walter Reed Army Institute of Research
Gina C. Donofrio: Henry M. Jackson Foundation for the Advancement of Military Medicine
Ningbo Jian: Henry M. Jackson Foundation for the Advancement of Military Medicine
Hannah A. D. King: Henry M. Jackson Foundation for the Advancement of Military Medicine
Cynthia G. Lorang: National Institutes of Health
Elizabeth J. Martinez: Walter Reed Army Institute of Research
Phyllis A. Rees: Walter Reed Army Institute of Research
Caroline E. Peterson: Walter Reed Army Institute of Research
Fabian Schmidt: The Rockefeller University
Tricia J. Hart: Trudeau Institute
Debra K. Duso: Trudeau Institute
Lawrence W. Kummer: Trudeau Institute
Sean P. Casey: Trudeau Institute
Jazmean K. Williams: Integral Molecular
Shruthi Kannan: Integral Molecular
Bonnie M. Slike: Henry M. Jackson Foundation for the Advancement of Military Medicine
Lauren Smith: Henry M. Jackson Foundation for the Advancement of Military Medicine
Isabella Swafford: Henry M. Jackson Foundation for the Advancement of Military Medicine
Paul V. Thomas: Walter Reed Army Institute of Research
Ursula Tran: Henry M. Jackson Foundation for the Advancement of Military Medicine
Jeffrey R. Currier: Walter Reed Army Institute of Research
Diane L. Bolton: Henry M. Jackson Foundation for the Advancement of Military Medicine
Edgar Davidson: Integral Molecular
Benjamin J. Doranz: Integral Molecular
Theodora Hatziioannou: The Rockefeller University
Paul D. Bieniasz: The Rockefeller University
Dominic Paquin-Proulx: Henry M. Jackson Foundation for the Advancement of Military Medicine
William W. Reiley: Trudeau Institute
Morgane Rolland: Walter Reed Army Institute of Research
Nancy J. Sullivan: National Institutes of Health
Sandhya Vasan: Walter Reed Army Institute of Research
Natalie D. Collins: Walter Reed Army Institute of Research
Kayvon Modjarrad: Walter Reed Army Institute of Research
Gregory D. Gromowski: Walter Reed Army Institute of Research
Victoria R. Polonis: Walter Reed Army Institute of Research
Nelson L. Michael: Walter Reed Army Institute of Research
Shelly J. Krebs: Walter Reed Army Institute of Research
M. Gordon Joyce: Walter Reed Army Institute of Research

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.

Date: 2024
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DOI: 10.1038/s41467-023-44265-0

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