Nature Communications (Jan 2024)

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,
  • M. Gordon Joyce

DOI
https://doi.org/10.1038/s41467-023-44265-0
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 19

Abstract

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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.