SARS-CoV-2 neutralizing antibody epitopes are overlapping and highly
mutated which raises the chances of escape variants and requires
development of broadly reactive vaccines
Abstract
The rapid adaptation of SARS-CoV-2 within the host species and the
increased viral transmission triggered the evolution of different
SARS-CoV-2 variants. Though numerous monoclonal antibodies (mAbs) have
been identified as prophylactic therapy for SARS-CoV-2, the ongoing
surge in the number of SARS-CoV-2 infections shows the importance of
understanding the mutations in the spike and developing novel vaccine
strategies to target all variants. Here, we report the map of
experimentally validated 74 SARS-CoV-2 neutralizing mAb binding epitopes
of all variants. The majority (87.84%) of the potent neutralizing
epitopes are localized to the receptor-binding domain (RBD) and overlap
with each other, whereas limited (12.16%) epitopes are found in the
N-terminal domain (NTD). Notably, 69 out of 74 mAb targets have at least
one mutation at the epitope sites. The potent epitopes found in the RBD
show higher mutations (4-10aa) compared to lower or modest neutralizing
antibodies, suggesting that these epitopes might co-evolve with the
immune pressure. The current study shows the importance of determining
the critical mutations at the antibody recognition epitopes, leading to
the development of broadly reactive immunogens targeting multiple
SARS-CoV-2 variants. Further, vaccines inducing both humoral and
cell-mediated immune responses might prevent the escape of SARS-CoV-2
variants from neutralizing antibodies.