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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2024-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-44265-0
_version_ 1797363145287663616
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
work_keys_str_mv AT rajeshwerssankhala diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT kerriglal diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT jaimeljensen diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT vincentdussupt diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT letzibethmendezrivera diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT hongjunbai diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT lindsaywieczorek diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT sandravmayer diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT michellezemil diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT danielleawagner diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT samanthamtownsley diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT agneshajduczki diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT williamcchang diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT weihungchen diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT ginacdonofrio diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT ningbojian diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT hannahadking diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT cynthiaglorang diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT elizabethjmartinez diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT phyllisarees diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT carolineepeterson diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT fabianschmidt diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT triciajhart diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT debrakduso diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT lawrencewkummer diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT seanpcasey diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT jazmeankwilliams diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT shruthikannan diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT bonniemslike diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT laurensmith diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT isabellaswafford diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT paulvthomas diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT ursulatran diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT jeffreyrcurrier diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT dianelbolton diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT edgardavidson diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT benjaminjdoranz diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT theodorahatziioannou diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT pauldbieniasz diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT dominicpaquinproulx diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT williamwreiley diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT morganerolland diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT nancyjsullivan diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT sandhyavasan diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT nataliedcollins diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT kayvonmodjarrad diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT gregorydgromowski diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT victoriarpolonis diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT nelsonlmichael diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT shellyjkrebs diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques
AT mgordonjoyce diversearrayofneutralizingantibodieseliciteduponspikeferritinnanoparticlevaccinationinrhesusmacaques