1. Site-directed neutralizing antibodies targeting structural sites on SARS-CoV-2 spike protein.
- Author
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Li, Xiaofeng, Kulakova, Liudmila, Jones, Kezzia, Toth, Eric A., Mitchell, Marina Kirkland, Mendez, Qiana, Weiner, Michael P., and Fuerst, Thomas R.
- Subjects
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SARS-CoV-2 Omicron variant , *AMINO acid separation , *MONOCLONAL antibodies , *SARS-CoV-2 , *IMMUNOGLOBULINS , *PEPTIDES - Abstract
'Epivolve' (epi tope e vol ution) is an innovative paratope-evolving technology using a haptenated peptide or protein immunogen as a means of directing the in vivo immune response to specifically targeted sites at a one amino acid residue resolution. Guided by protein structural analysis, Epivolve technology was tested to develop site-directed neutralizing antibodies (nAbs) in a systematic fashion against the SARS-CoV-2 Receptor Binding Domain (RBD). Thirteen solvent-exposed sites covering the ACE2 receptor-binding interface were targeted. Immunogens composed of each targeted site were used to immunize rabbits in separate cohorts. In vivo site-directed immune responses against all 13 targets were demonstrated by B cell secreted IgG and recombinant IgG testing. One site, SL13 (Y505) which mutates from tyrosine to histidine in the SARS-CoV-2 Omicron variant, was chosen as a proof-of-concept (PoC) model for further functional monoclonal antibody development. Epivolve technology demonstrated the capabilities of generating pan-variant antibodies and nAbs against the SARS-CoV-2 primary strain and the Omicron variant. • Epivolve is an innovative technology to develop site-directed antibodies. • Thirteen site-directed antibodies cover SARS-CoV-2 RBD and ACE2 structural interface. • SARS-CoV-2 neutralizing antibodies targeting SL13 (Y505) site is pan-variant. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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