A. A schematic representation of chimeric and inferred germline (iGL) reverted antibodies. The mature antibody, referred to as ‘Mat’ shows constant region (grey), the variable heavy (VH) chain (red) and variable light (VL) chain (green). The third Complementarity Determining Regions of VH (CDRH3) and VL (CDRL3) chains are shown at the end of each variable region. The VH and VL genes are further divided into framework regions (FR1-3) and other CDRs (CDR1-2) shown with ImMunoGeneTics (IMGT) numbering. To generate the VH or VL regions in iGL Abs were replaced in with their closest inferred germline sequence predicted by in the IMGT human IgG germline database (Brochet et al., 2008). The CDRH3 and CDRL3 from the Mat antibodies were retained in the reverted iGL Abs.
B. Association of IC50 neutralization titers with number of somatic mutations in VH and VL for the four prototype Abs, PG9, CH01, CAP256.09 and PGT145.
C. Neutralization breadth of Mat, chimeric and iGL reverted V2 apex bnAbs. The number of viruses in an 18-virus panel neutralized with an IC50 <10 μg/ml is shown for Mat and chimeric Abs. For the less potent iGL Abs, neutralization is scored as positive with IC50 <100 μg/ml.