학술논문
Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques
Document Type
article
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
Source
Nature Communications, Vol 15, Iss 1, Pp 1-19 (2024)
Subject
Language
English
ISSN
2041-1723
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.