8FHY

Crystal structure of the SARS-CoV-2 receptor binding domain in complex with neutralizing antibody WRAIR-5021

Summary for 8FHY

• Entry DOI: 10.2210/pdb8fhy/pdb
• Descriptor: Spike protein S1, WRAIR-5021 Fab Light chain, WRAIR-5021 Fab Heavy chain, ... (7 entities in total)
• Functional Keywords: sars-cov-2, viral protein, immune system, rbd, antibody, nonhuman primate, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 2019-nCoV, COVID-19 virus); More
• Total number of polymer chains: 9
• Total formula weight: 212441.57

Authors

Sankhala, R.S.,Jensen, J.L.,Joyce, M.G. (deposition date: 2022-12-15, release date: 2024-01-17, Last modification date: 2024-11-20)

Primary citation

Sankhala, R.S.,Lal, K.G.,Jensen, J.L.,Dussupt, V.,Mendez-Rivera, L.,Bai, H.,Wieczorek, L.,Mayer, S.V.,Zemil, M.,Wagner, D.A.,Townsley, S.M.,Hajduczki, A.,Chang, W.C.,Chen, W.H.,Donofrio, G.C.,Jian, N.,King, H.A.D.,Lorang, C.G.,Martinez, E.J.,Rees, P.A.,Peterson, C.E.,Schmidt, F.,Hart, T.J.,Duso, D.K.,Kummer, L.W.,Casey, S.P.,Williams, J.K.,Kannan, S.,Slike, B.M.,Smith, L.,Swafford, I.,Thomas, P.V.,Tran, U.,Currier, J.R.,Bolton, D.L.,Davidson, E.,Doranz, B.J.,Hatziioannou, T.,Bieniasz, P.D.,Paquin-Proulx, D.,Reiley, W.W.,Rolland, M.,Sullivan, N.J.,Vasan, S.,Collins, N.D.,Modjarrad, K.,Gromowski, G.D.,Polonis, V.R.,Michael, N.L.,Krebs, S.J.,Joyce, M.G.
Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques.
Nat Commun, 15:200-200, 2024

PubMed 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.

PubMed: 38172512
DOI: 10.1038/s41467-023-44265-0

Experimental method

X-RAY DIFFRACTION (2.53 Å)