Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein

0572379 - BC 2024 RIV US eng J - Journal Article
Bianchini, F. - Crivelli, V. - Abernathy, M. R. - Guerra, C. - Palus, Martin - Muri, J. - Marcotte, H. - Piralla, A. - Pedotti, M. - De Gasparo, R. - Simonelli, L. - Matkovic, M. - Toscano, C. - Biggiogero, M. - Calvaruso, V. - Svoboda, Pavel - Rincon, T. C. - Fava, T. - Podesvova, L. - Shanbhag, A. A. - Celoria, A. - Sgrignani, J. - Štefánik, M. - Hönig, Václav - Prančlová, Veronika - Michalčíková, Tereza - Procházka, Jan - Guerrini, G. - Mehn, D. - Clabbattini, A. - Sedláček, Radislav - Růžek, Daniel … Total 46 authors
Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein.
SCI IMMUNOL. Roč. 8, č. 81 (2023), č. článku eade0958. ISSN 2470-9468. E-ISSN 2470-9468
R&D Projects: GA MŠMT(CZ) LX22NPO5103; GA ČR(CZ) GF21-05445L; GA ČR GF22-17139K; GA MŠMT(CZ) LM2018126
Research Infrastructure: Czech-BioImaging II - 90129
Institutional support: RVO:60077344 ; RVO:68378050
Keywords : SARS-CoV-2 * glycoprotein * epitopes
OECD category: Virology; Immunology (UMG-J)
Impact factor: 24.8, year: 2022
Method of publishing: Open access
https://www.science.org/doi/10.1126/sciimmunol.ade0958

Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2 ' site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization, and, similar to fp.006 and hr2.016, protects mice expressing human angiotensin-converting enzyme 2 against infection when present as a bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are crossreactive with Orthocoronavirinae, including SARS-CoV-2 variants.
Permanent Link: https://hdl.handle.net/11104/0343705