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. ReesCaroline 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number200
JournalNature Communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024
Externally publishedYes

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