A. High-throughput SPR was used to determine the
competitive relationship between 186 RBD-directed mAbs. The dataset was analyzed
by Carterra Epitope software to sort competition profiles of clones into related
clusters, which are represented as shared colored regions of the dendrogram. The
RBD epitope landscape can be broadly divided into seven communities containing
mAbs that bind the receptor-binding motif (RBD-1 through RBD-3), the outer face
of the RBD (RBD-4 and RBD-5) or the inner face of the RBD (RBD-6 and RBD-7).
Communities can be further divided into smaller clusters (e.g., RBD-2a and
−2b) and bins (e.g., RBD-2b.1, −2b.2 and −2b.3) based on
their discrete competition with other clusters and/or their ability to compete
with ACE2 for Spike binding. Black bars indicate single clones that were used in
further analyses. Table
S1 lists additional metrics for the indicated mAbs (i.e., ACE2
blocking, kinetic analyses and germline information) and detailed information
for the entire CoVIC panel is at covic.lji.org. B. Binary heat-map matrix
demonstrating the competition profile for the finer clusters and bins for the
subset of single clones indicated by black bars in panel A. The matrix here
contains representative examples. The complete competition matrix for the study
is in Table S2. RBD-2
can be divided into clusters “a” and “b”, which have
varying ability to compete with mAbs in RBD-4 (e.g., RBD-2a mAbs do not compete
while most RBD-2b mAbs do). Cluster RBD-2b can be divided into three smaller
bins that vary in their competition with both RBD-3 and RBD-4 mAbs: those in
2b.1, but not 2b.2 or 2b.3, compete with RBD-3 mAbs whereas mAbs in 2b.1 and
2b.2, but not 2b.3, compete with RBD-4 mAbs. RBD-4 contains mAbs that do
(RBD-4a) and do not (RBD-4b) compete with ACE2. RBD-5 and RBD-7 have clusters of
mAbs with lower neutralizing potency (i.e., RBD-5c and RBD-7b and RBD-7c)
relative to the other cluster in the same community (i.e., RBD-5a and RBD-5b and
RBD-7a). Rows and columns indicate the immobilized mAb and injected analyte mAb,
respectively. Table S2
shows the complete matrix for competition between all 186 mAbs.