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- Title
Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques.
- Authors
Sankhala, Rajeshwer S.; Lal, Kerri G.; Jensen, Jaime L.; Dussupt, Vincent; Mendez-Rivera, Letzibeth; Bai, Hongjun; Wieczorek, Lindsay; Mayer, Sandra V.; Zemil, Michelle; Wagner, Danielle A.; Townsley, Samantha M.; Hajduczki, Agnes; Chang, William C.; Chen, Wei-Hung; Donofrio, Gina C.; Jian, Ningbo; King, Hannah A. D.; Lorang, Cynthia G.; Martinez, Elizabeth J.; Rees, Phyllis A.
- 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. An adjuvanted SARS-CoV-2 spike-ferritin nanoparticle vaccine can elicit antibodies with relatively broad sarbecovirus activity in non-human primates. Here, the authors isolate and structurally characterize several monoclonal antibodies providing insights into the targeted epitopes and broad reactivity.
- Subjects
MONOCLONAL antibodies; RHESUS monkeys; NANOPARTICLES; SARS-CoV-2 Omicron variant; IMMUNOGLOBULINS; FERRITIN; ANTIBODY formation; MACAQUES
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-44265-0