Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques
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 Fe...
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Nature Portfolio
2024-01-01
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Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/s41467-023-44265-0 |
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author | 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 M. Gordon Joyce |
author_facet | 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 M. Gordon Joyce |
author_sort | Rajeshwer S. Sankhala |
collection | DOAJ |
description | 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. |
first_indexed | 2024-03-08T16:16:18Z |
format | Article |
id | doaj.art-61dc74f1c5d84f64ac1178c032cab9f4 |
institution | Directory Open Access Journal |
issn | 2041-1723 |
language | English |
last_indexed | 2024-03-08T16:16:18Z |
publishDate | 2024-01-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Nature Communications |
spelling | doaj.art-61dc74f1c5d84f64ac1178c032cab9f42024-01-07T12:33:36ZengNature PortfolioNature Communications2041-17232024-01-0115111910.1038/s41467-023-44265-0Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaquesRajeshwer S. Sankhala0Kerri G. Lal1Jaime L. Jensen2Vincent Dussupt3Letzibeth Mendez-Rivera4Hongjun Bai5Lindsay Wieczorek6Sandra V. Mayer7Michelle Zemil8Danielle A. Wagner9Samantha M. Townsley10Agnes Hajduczki11William C. Chang12Wei-Hung Chen13Gina C. Donofrio14Ningbo Jian15Hannah A. D. King16Cynthia G. Lorang17Elizabeth J. Martinez18Phyllis A. Rees19Caroline E. Peterson20Fabian Schmidt21Tricia J. Hart22Debra K. Duso23Lawrence W. Kummer24Sean P. Casey25Jazmean K. Williams26Shruthi Kannan27Bonnie M. Slike28Lauren Smith29Isabella Swafford30Paul V. Thomas31Ursula Tran32Jeffrey R. Currier33Diane L. Bolton34Edgar Davidson35Benjamin J. Doranz36Theodora Hatziioannou37Paul D. Bieniasz38Dominic Paquin-Proulx39William W. Reiley40Morgane Rolland41Nancy J. Sullivan42Sandhya Vasan43Natalie D. Collins44Kayvon Modjarrad45Gregory D. Gromowski46Victoria R. Polonis47Nelson L. Michael48Shelly J. Krebs49M. Gordon Joyce50Emerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchHenry M. Jackson Foundation for the Advancement of Military MedicineEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchHenry M. Jackson Foundation for the Advancement of Military MedicineEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchHenry M. Jackson Foundation for the Advancement of Military MedicineVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthHenry M. Jackson Foundation for the Advancement of Military MedicineEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchHenry M. Jackson Foundation for the Advancement of Military MedicineHenry M. Jackson Foundation for the Advancement of Military MedicineHenry M. Jackson Foundation for the Advancement of Military MedicineVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchLaboratory of Retrovirology, The Rockefeller UniversityTrudeau InstituteTrudeau InstituteTrudeau InstituteTrudeau InstituteIntegral MolecularIntegral MolecularHenry M. Jackson Foundation for the Advancement of Military MedicineHenry M. Jackson Foundation for the Advancement of Military MedicineHenry M. Jackson Foundation for the Advancement of Military MedicineEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchHenry M. Jackson Foundation for the Advancement of Military MedicineViral Diseases Branch, Walter Reed Army Institute of ResearchHenry M. Jackson Foundation for the Advancement of Military MedicineIntegral MolecularIntegral MolecularLaboratory of Retrovirology, The Rockefeller UniversityLaboratory of Retrovirology, The Rockefeller UniversityHenry M. Jackson Foundation for the Advancement of Military MedicineTrudeau InstituteEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchViral Diseases Branch, Walter Reed Army Institute of ResearchU.S. Military HIV Research Program, Walter Reed Army Institute of ResearchCenter for Infectious Disease Research, Walter Reed Army Institute of ResearchEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchEmerging Infectious Diseases Branch, Walter Reed Army Institute of ResearchAbstract 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.https://doi.org/10.1038/s41467-023-44265-0 |
spellingShingle | 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 M. Gordon Joyce Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques Nature Communications |
title | Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques |
title_full | Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques |
title_fullStr | Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques |
title_full_unstemmed | Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques |
title_short | Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques |
title_sort | diverse array of neutralizing antibodies elicited upon spike ferritin nanoparticle vaccination in rhesus macaques |
url | https://doi.org/10.1038/s41467-023-44265-0 |
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