SARS-CoV-2 receptor binding mutations and antibody mediated immunity

Abstract

SARS-CoV-2 mutations can impact infectivity, viral load, and overall morbidity/mortality during infection. In this analysis, we look at the mutational landscape of the SARS-CoV-2 receptor binding domain, a structure that is antigenic and allows for viral binding to the host. We analyze 104193 GISAID sequences acquired on October 15th, 2020 with a majority of sequences (96%) containing point mutations. We report high frequency mutations with improved binding affinity to ACE2 including S477N, N439K, V367F, and N501Y and address the potential impact of RBD mutations on antibody binding. The high frequency S477N mutation is present in 6.7% of all SARS-CoV-2 sequences, co-occurs with D614G, and is currently present in 14 countries. To address RBD-antibody interactions we take a subset of human derived antibodies and define their interacting residues using PDBsum. Our analysis shows that adaptive immunity against SARS-CoV-2 enlists broad coverage of the RBD suggesting that antibody mediated immunity should be sufficient to resolve infection in the presence of RBD point mutations that conserve structure.

A single dose of the SARS-CoV-2 vaccine BNT162b2 elicits Fc-mediated antibody effector functions and T cell responses

“…Studies have shown that this mutation increases affinity of the S glycoprotein for ACE-2 (Nelson et al, 2021) and confers resistance to neutralization mediated by monoclonal antibodies (mAbs) and plasma from naturally infected and vaccinated individuals (Ku et al, 2021;Stamatatos et al, 2021;Tada et al, 2021;Wang et al, 2021). The S477N mutation confers a higher affinity for the ACE-2 receptor and has rapidly spread to many countries in Oceania and Europe (Flores-Alanis et al, 2021;Hodcroft et al, 2020;Jolly et al, 2021;Mejdani et al, 2021;West et al, 2021;Wu et al, 2021). The S477N and N501S mutations are found in several SARS-CoV-2 genomes in Quebec (S.M.…”

A single BNT162b2 mRNA dose elicits antibodies with Fc-mediated effector functions and boost pre-existing humoral and T cell responses

“…Studies have shown that this mutation increases affinity of the S glycoprotein for ACE-2 18 and confers resistance to neutralization mediated by mAbs and plasma from naturally-infected and vaccinated individuals 19–22 . The S477N mutation confers a higher affinity for the ACE-2 receptor and has rapidly spread to many countries in Oceania and Europe 23–28 . The S477N and N501S mutations are found in several SARS-CoV-2 genomes in Quebec (Laboratoire de Santé Publique du Québec, unpublished data).…”

Evolutionary trajectory of SARS-CoV-2 and emerging variants

“…A701V, shared by variant B.1.351 [100], is in the S2 subunit adjacent to the furin cleavage site [219] and may impact SARS-CoV-2 cleavability and infectivity. S477N, also found in variant 20A.EU2, increases binding to hACE2 [221,222] and reduces antibody-mediated neutralization [178,223], likely due to its position within a neutralizing epitope [224]. D614G and E484K are shared with multiple other variants (Table 5 [183,225].…”