1. Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques.
- Author
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Sankhala RS, Lal KG, Jensen JL, Dussupt V, Mendez-Rivera L, Bai H, Wieczorek L, Mayer SV, Zemil M, Wagner DA, Townsley SM, Hajduczki A, Chang WC, Chen WH, Donofrio GC, Jian N, King HAD, Lorang CG, Martinez EJ, Rees PA, Peterson CE, Schmidt F, Hart TJ, Duso DK, Kummer LW, Casey SP, Williams JK, Kannan S, Slike BM, Smith L, Swafford I, Thomas PV, Tran U, Currier JR, Bolton DL, Davidson E, Doranz BJ, Hatziioannou T, Bieniasz PD, Paquin-Proulx D, Reiley WW, Rolland M, Sullivan NJ, Vasan S, Collins ND, Modjarrad K, Gromowski GD, Polonis VR, Michael NL, Krebs SJ, and Joyce MG
- Subjects
- Animals, Mice, Antibodies, Neutralizing, Macaca mulatta, Vaccination, Antibodies, Viral, Antibodies, Monoclonal, COVID-19 Vaccines, Ferritins, Spike Glycoprotein, Coronavirus genetics, Nanoparticles, Severe acute respiratory syndrome-related coronavirus
- 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., (© 2024. The Author(s).)
- Published
- 2024
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