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Macaque study finds CD4 binding site antibodies close to inferred unmutated ancestor

The surprising thing for me is that the naive precursors for these CD4 binding site antibodies bound well. This is in contrast to the V1-V2 binding human bNAbs found, say, in Doria-Rose et al 2014 and other papers. Different animal and different antibodies.

They inferred unmutated ancestors (UAs), which for some reason they call igLs, by taking a consensus of similar-looking sequences: “Based on HCDR3 length and homology, as well as by use of the same V and J germlines, we identified related sibling clones.” They could not find anything close to the UA in the pre-vaccination repertoire.

Rather than just doing ELISAs, they also did Biolayer Light Interferometry with Octet, which IIUC directly measures binding through time to get a clearer picture of on and off rates.

As a reminder, here’s a map of the various binding sites from a nice review.