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Mol Cell ; 81(24): 5099-5111.e8, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1578079


The SARS-CoV-2 spike protein is a critical component of vaccines and a target for neutralizing monoclonal antibodies (nAbs). Spike is also undergoing immunogenic selection with variants that increase infectivity and partially escape convalescent plasma. Here, we describe Spike Display, a high-throughput platform to rapidly characterize glycosylated spike ectodomains across multiple coronavirus-family proteins. We assayed ∼200 variant SARS-CoV-2 spikes for their expression, ACE2 binding, and recognition by 13 nAbs. An alanine scan of all five N-terminal domain (NTD) loops highlights a public epitope in the N1, N3, and N5 loops recognized by most NTD-binding nAbs. NTD mutations in variants of concern B.1.1.7 (alpha), B.1.351 (beta), B.1.1.28 (gamma), B.1.427/B.1.429 (epsilon), and B.1.617.2 (delta) impact spike expression and escape most NTD-targeting nAbs. Finally, B.1.351 and B.1.1.28 completely escape a potent ACE2 mimic. We anticipate that Spike Display will accelerate antigen design, deep scanning mutagenesis, and antibody epitope mapping for SARS-CoV-2 and other emerging viral threats.

Mammals/virology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Animals , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/virology , Cell Line , Epitopes/genetics , Epitopes/immunology , HEK293 Cells , Humans , Mammals/immunology , Protein Binding/genetics , Protein Binding/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology
Commun Biol ; 4(1): 1196, 2021 10 13.
Article in English | MEDLINE | ID: covidwho-1467140


Emerging mutations in SARS-CoV-2 cause several waves of COVID-19 pandemic. Here we investigate the infectivity and antigenicity of ten emerging SARS-CoV-2 variants-B.1.1.298, B.1.1.7(Alpha), B.1.351(Beta), P.1(Gamma), P.2(Zeta), B.1.429(Epsilon), B.1.525(Eta), B.1.526-1(Iota), B.1.526-2(Iota), B.1.1.318-and seven corresponding single amino acid mutations in the receptor-binding domain using SARS-CoV-2 pseudovirus. The results indicate that the pseudovirus of most of the SARS-CoV-2 variants (except B.1.1.298) display slightly increased infectivity in human and monkey cell lines, especially B.1.351, B.1.525 and B.1.526 in Calu-3 cells. The K417N/T, N501Y, or E484K-carrying variants exhibit significantly increased abilities to infect mouse ACE2-overexpressing cells. The activities of furin, TMPRSS2, and cathepsin L are increased against most of the variants. RBD amino acid mutations comprising K417T/N, L452R, Y453F, S477N, E484K, and N501Y cause significant immune escape from 11 of 13 monoclonal antibodies. However, the resistance to neutralization by convalescent serum or vaccines elicited serum is mainly caused by the E484K mutation. The convalescent serum from B.1.1.7- and B.1.351-infected patients neutralized the variants themselves better than other SARS-CoV-2 variants. Our study provides insights regarding therapeutic antibodies and vaccines, and highlights the importance of E484K mutation.

COVID-19/virology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Animals , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/therapy , Cell Line , HEK293 Cells , Humans , Immunization, Passive/methods , Mammals/immunology , Mice , Mutation , Pandemics , Primates/immunology , Protein Binding , Tropism/genetics
Int Immunopharmacol ; 85: 106654, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-505643


The present state of diagnostic and therapeutic developmental race for vaccines against the SARS CoV-2 (nCOVID-19) focuses on prevention and control of this global pandemic which also represents a critical challenge to the global health community. Although development of novel vaccines can prevent the SARS CoV-2 infections, it is still impeded by several other factors and therefore novel approaches towards treatment and management of this disease is the urgent need. Passive immunotherapy plays a vital role as a possible alternative to meet this challenge and among various antibody sources, chicken egg yolk antibodies (IgY) can be used as an alternative to mammalian antibodies which have been previously studied against SARS CoV outbreak in China. In this review, we discuss the strategies for the use of chicken egg yolk (IgY) antibodies in the development of rapid diagnosis and immunotherapy against SARS CoV-2. Also, IgY antibodies have previously been used against various respiratory bacterial and viral infections in humans and animals. Compared to mammalian antibodies (IgG), chicken egg yolk antibodies (IgY) have greater binding affinity to specific antigens, ease of extraction and lower production costs, hence possessing remarkable pathogen-neutralizing activity of pathogens in respiratory and lungs. We provide an overall importance for the use of monoclonal chicken egg yolk antibodies (IgY) using phage display method describing their potential passive immunotherapeutic application for the treatment and prevention of SARS CoV-2 infection which is simple, fast and safe way of approach for treating patients effectively.

Antibodies, Monoclonal/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Cell Surface Display Techniques , Clinical Laboratory Techniques , Coronavirus Infections , Immunoglobulins/immunology , Pandemics , Pneumonia, Viral , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibody Affinity , Antibody Specificity , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , Chickens , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Egg Yolk , Forecasting , Humans , Immunization, Passive , Mammals/immunology , Models, Molecular , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , RNA, Viral/genetics , SARS-CoV-2 , Single-Chain Antibodies/immunology , Species Specificity , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism