Discovery of antibodies that may eliminate the need for COVID vaccines Antibodies Coronavirus Disease COVID TelAvivUni CommsBio
By Pooja Toshniwal PahariaSep 11 2022Reviewed by Danielle Ellis, B.Sc. In a recent study published in the journal Communications Biology, researchers evaluated the efficacy of monoclonal antibodies from severe acute respiratory syndrome coronavirus 2 ancestral Wuhan-1-strain-infected convalescent donors against SARS-CoV-2 VOCs such as Alpha, Beta, Gamma, Delta, and Omicron.
The authors of the present study previously identified nine SARS-CoV-2 neutralizing mAbs from the sera of two coronavirus disease 2019 convalescents infected probably with the ancestral strain. Of these, seven mAbs demonstrated potent SARS-CoV-2 neutralization, whereas the remaining two mAbs showed lower potency.
Flow cytometry analysis was performed to assess mAbs’ ability to inhibit binding interactions between human angiotensin-converting enzyme 2 and S proteins of the ancestral strain and Alpha, Beta, and Delta VOCs. In addition, prevention of SARS-CoV-2 infection by mAbs was assessed by pseudovirus and authentic virus neutralization assays using Vero-TMPRSS2 cells.
The L452R mutation and E484K mutation majorly impacted Ab binding. Further, RBDs comprising N439K, Y453F, and A475V single mutations showed binding with all mAbs as efficiently as with the ancestral strain RBD. TAU-2303 binding to the K417N/N501Y doubly mutated RBD was decreased, although the mutations showed no significant effect individually.
The combination of RBD mutations may alter SARS-CoV-2 resistance; Omicron has mutations in seven residues in the Fab2303 binding epitope, including Q493, Q498, Y505, and K417, providing the structural explanation for the lack of Omicron neutralization by the TAU-2303 mAb. The E484K mutation disrupted hydrogen bonds between the TAU-2212 and the RBD, providing a structural explanation for the lack of Beta and Gamma VOC neutralization by TAU-2212.