Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses

Chen, Yanjia; Zhao, Xiaoyu; Zhou, Hao; Zhu, Hengrui; Jiang, Shibo; Wang, Pengfei

doi:10.1038/s41577-022-00784-3

Cited by 200 publications

(212 citation statements)

References 116 publications

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“…All of these subvariants exhibit some degree of enhanced neutralization resistance over their parental BA.4/5 or BA. (Chen et al, 2022;Su et al, 2022a). As circulating SARS-CoV-2 diversifies, the ability to vaccinate against dominant circulating variants may be even more compromised.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the strong evasion of BA.4/5 infection-induced sera is concerning, as the recently recommended bivalent mRNA vaccine boosters contain BA.4/5 S along with the prototype. This possibility, together with the emergence of more diverse SARS-CoV-2 variants necessitates the development of more broadly active, even pan-coronavirus, COVID-19 vaccines (Chen et al, 2022; Su et al, 2022a). As circulating SARS-CoV-2 diversifies, the ability to vaccinate against dominant circulating variants may be even more compromised.…”

Section: Discussionmentioning

confidence: 99%

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Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2

Evans

Faraone

et al. 2022

Preprint

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Continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants including BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2. Here we examine the neutralization resistance of these subvariants as well as their ancestral BA.4/5, BA.2.75 and D614G variants against sera from 3-dose vaccinated health care workers, hospitalized BA.1-wave patients, and BA.5-wave patients. We found enhanced neutralization resistance in all new subvariants, especially the BQ.1 and BQ.1.1 subvariants driven by a key N460K mutation and to a lesser extent, R346T and K444T mutations, as well as the BA.2.75.2 subvariant driven largely by its key F486S mutation. The BQ.1 and BQ.1.1 subvariants also exhibited enhanced fusogenicity and S processing dictated by the key N460K mutation. Interestingly, the BA.2.75.2 subvariant saw an enhancement by the F486S mutation and a reduction by the D1199N mutation to its fusogenicity and S processing resulting in minimal overall change. Molecular modelling revealed the mechanisms of receptor-binding and non-receptor binding monoclonal antibody-mediated immune evasion by R346T, K444T, F486S and D1199N mutations. Altogether, these findings shed light on the concerning evolution of newly emerging SARS-CoV-2 Omicron subvariants.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2

Evans

Faraone

et al. 2022

Preprint

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“…Neutralizing antibodies that target the S2 region and act in the post-attachment phase were recently described. Although generally weak neutralizers, some display broad reactivity against SARS-CoV-2 variants, and even against more distant CoV species ( 16–20, 41, 42 ), which is analogous to what is observed with antibodies that target the FP of influenza and HIV-1 ( 43–45 ).…”

Section: Discussionmentioning

confidence: 55%

Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2

Bianchini

Crivelli

Abernathy

et al. 2022

Preprint

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Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the fourgenera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2’ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive withOrthocoronavirinae, including SARS-CoV-2 variants.One sentence summaryBroadly cross-reactive antibodies that protect from SARS-CoV-2 variants are revealed by virus coldspot-driven discovery.

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“…Four antibodies responsive to the earlier SARS-CoV-2 variant (WA-1) have been reported to be able to interact with a wide range of variants of concern (VOCs) [8]. The antibodies against different VOCs are readily found to suggest that antibodies with broad neutralization may exist [9][10][11][12][13]. On the other hand, convergent antibodies reactive to SARS-CoV-2 from different infected subjects suggest the diversified immune response against the SARS-CoV-2 may share similar clonotypes [3,14].…”

Section: Introductionmentioning

confidence: 99%

The Longitudinal Analysis of Convergent Antibody VDJ Regions in SARS-CoV-2 Positive Patients Using RNA-seq

Liu

Zelazowska

McBride

2022

Preprint

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The severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has infected over 600 million individuals and caused over 6.5 million deaths. To understand the immune response individuals have from the SARS-CoV-2 infection, we studied the immunoglobulins against the viral antigens. The diversified complementarity determining region 3 (CDR3) can be used to characterize an antibody. We downloaded four public RNA-seq data sets that were collected between March 2020 and March 2022 from the Gene Expression Omnibus (GEO) in our longitudinal analysis. In total, there were 269 SARS-CoV-2 positive patients and 26 negative patients who served as a control group. Samples were grouped based on their SARS-CoV-2 variant type and/or the time they were collected. Among 629,137 immunoglobulin V(D)J sequences identified by reconstructing the V(D)J sequences, we found 1011 common V(D)Js (same V gene, J gene and CDR3 sequences in each SARS-CoV-2 positive group) shared by more than one patient in each group and no common V(D)Js were from the negative control group. In our clustering analysis, we identified 129 convergent clusters from the SARS-CoV-2 positive groups. One of these convergent clusters matched the protein sequence of crystal 3D structures of the antibodies against SARS-CoV-2 in the Protein Data Bank (PDB). In our longitudinal analysis between the Alpha and Omicron variant, we found 2.7% of common CDR3s were shared although the longitudinal profiling of common V(D)Js was variant specific. Although diverse immunoglobulin profiles were observed, the convergence of common V(D)Js suggests that there exists antibodies with similar antigenic specificities across patients in different groups over various stages of the pandemic.

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Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses

Cited by 200 publications

References 116 publications

Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2

Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2

Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2

The Longitudinal Analysis of Convergent Antibody VDJ Regions in SARS-CoV-2 Positive Patients Using RNA-seq

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