TY - JOUR
T1 - A human monoclonal antibody neutralizing SARS-CoV-2 Omicron variants containing the L452R mutation
AU - Stein, Saskia C.
AU - Hansen, Guido
AU - Ssebyatika, George
AU - Ströh, Luisa J.
AU - Ochulor, Okechukwu
AU - Herold, Elisabeth
AU - Schwarzloh, Britta
AU - Mutschall, Doris
AU - Zischke, Jasmin
AU - Cordes, Anne K.
AU - Schneider, Talia
AU - Hinrichs, Imke
AU - Blasczyk, Rainer
AU - Kleine-Weber, Hannah
AU - Hoffmann, Markus
AU - Klein, Florian
AU - Kaiser, Franziska K.
AU - Gonzalez-Hernandez, Mariana
AU - Armando, Federico
AU - Ciurkiewicz, Malgorzata
AU - Beythien, Georg
AU - Pöhlmann, Stefan
AU - Baumgärtner, Wolfgang
AU - Osterhaus, Albert
AU - Schulz, Thomas F.
AU - Krey, Thomas
N1 - Publisher Copyright:
Copyright © 2024 Stein et al.
PY - 2024/12
Y1 - 2024/12
N2 - The effectiveness of SARS-CoV-2 therapeutic antibodies targeting the spike (S) receptor-binding domain (RBD) has been hampered by the emergence of variants of concern (VOCs), which have acquired mutations to escape neutralizing antibodies (nAbs). These mutations are not evenly distributed on the RBD surface but cluster on several distinct surfaces, suggesting an influence of the targeted epitope on the capacity to neutralize a broad range of VOCs. Here, we identified a potent nAb from convalescent patients targeting the receptor-binding domain of a broad range of SARS-CoV-2 VOCs. Except for the Lambda and BA.2.86 variants, this nAb efficiently inhibited the entry of most tested VOCs, including Omicron subvariants BA.1, BA.2, XBB.1.5, and EG.5.1 and to a limited extent also BA.4/5, BA.4.6, and BQ.1.1. It bound recombinant S protein with picomolar affinity, reduced the viral load in the lung of infected hamsters, and prevented the severe lung pathology typical for SARS-CoV-2 infections. An X-ray structure of the nAb-RBD complex revealed an epitope that does not fall into any of the conventional classes and provided insights into its broad neutralization properties. Our findings highlight a conserved epitope within the SARS-CoV-2 RBD that should be preferably targeted by therapeutic antibodies and inform rational vaccine development.
AB - The effectiveness of SARS-CoV-2 therapeutic antibodies targeting the spike (S) receptor-binding domain (RBD) has been hampered by the emergence of variants of concern (VOCs), which have acquired mutations to escape neutralizing antibodies (nAbs). These mutations are not evenly distributed on the RBD surface but cluster on several distinct surfaces, suggesting an influence of the targeted epitope on the capacity to neutralize a broad range of VOCs. Here, we identified a potent nAb from convalescent patients targeting the receptor-binding domain of a broad range of SARS-CoV-2 VOCs. Except for the Lambda and BA.2.86 variants, this nAb efficiently inhibited the entry of most tested VOCs, including Omicron subvariants BA.1, BA.2, XBB.1.5, and EG.5.1 and to a limited extent also BA.4/5, BA.4.6, and BQ.1.1. It bound recombinant S protein with picomolar affinity, reduced the viral load in the lung of infected hamsters, and prevented the severe lung pathology typical for SARS-CoV-2 infections. An X-ray structure of the nAb-RBD complex revealed an epitope that does not fall into any of the conventional classes and provided insights into its broad neutralization properties. Our findings highlight a conserved epitope within the SARS-CoV-2 RBD that should be preferably targeted by therapeutic antibodies and inform rational vaccine development.
UR - https://www.scopus.com/pages/publications/85212926549
U2 - 10.1128/jvi.01223-24
DO - 10.1128/jvi.01223-24
M3 - Journal articles
C2 - 39494911
AN - SCOPUS:85212926549
SN - 0022-538X
VL - 98
JO - Journal of Virology
JF - Journal of Virology
IS - 12
ER -
