Antibodies with potent and broad neutralizing activity against antigenically diverse and highly transmissible SARS-CoV-2 variants

Wang, Lingshu; Zhou, Tongqing; Zhang, Yi; Yang, Eun Sung; Schramm, Chaim A.; Shi, Wei; Pegu, Amarendra; Oloninyi, Olamide K.; Ransier, Amy; Darko, Samuel; Narpala, Sandeep; Hatcher, Christian; Martinez, David R.; Tsybovsky, Yaroslav; Phung, Emily; Abiona, Olubukola M.; Cale, Evan M.; Chang, Lauren; Corbett, Kizzmekia S.; DiPiazza, Anthony; Gordon, Ingelise J.; Leung, Kwanyee; Liu, Tracy; Mason, Rosemarie D.; Nazzari, Alexandra; Novik, Laura; Olia, Adam S.; Stephens, Tyler; Stringham, Christopher D.; Talana, Chloe Adrienna; Teng, I-Ting; Wagner, Danielle A.; Widge, Alicia T.; Zhang, Baoshan; Ledgerwood, Julie E.; Ruckwardt, Tracy J.; Gaudinski, Martin R.; Baric, Ralph S.; Graham, Barney S.; McDermott, Adrian B.; Douek, Daniel C.; Kwong, Peter D.; Mascola, John R.; Sullivan, Nancy J.

doi:10.1101/2021.02.25.432969

Cited by 23 publications

(24 citation statements)

References 29 publications

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“…6c). All these emerging viral lineages except B.1.1.7 14,16,39,40 have a mutation that escapes some antibodies from at least one class. The class 2 antibody escape mutation E484K is present in the B.1.351, P.1, P.2, and B.1.526 lineages (Fig.…”

Section: Resultsmentioning

confidence: 99%

Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies

et al. 2021

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Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.

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Section: Resultsmentioning

confidence: 99%

Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies

et al. 2021

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“…We also examined the presence of escape mutations for each antibody class in some key emerging viral lineages ( Figure 6C ). All these emerging viral lineages except B.1.1.7 14,16,[39][40][41] have a mutation that escapes some antibodies from at least one class. The class 2 antibody escape mutation E484K is present in the B.1.351, P.1, P.2 and B.1.526 lineages ( Figure 6C ) 1,2,[4][5][6] .…”

Section: Mutations That Reduce Binding By Class 1 and 2 Antibodies Armentioning

confidence: 99%

Mutational escape from the polyclonal antibody response to SARS-CoV-2 infection is largely shaped by a single class of antibodies

Greaney

Starr

Barnes

et al. 2021

Preprint

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Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasma, including plasma from individuals from whom some of the antibodies were isolated. The plasma-escape maps most closely resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is dominated by a single class of antibodies targeting an epitope that is already undergoing rapid evolution.

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“…K417N and E484K in VOCs B.1.351 and P.1 have been reported to decrease the neutralizing activity of sera as well as neutralizing monoclonal antibodies isolated from COVID-19 convalescent plasma and vaccinated individuals (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62). B.1.351 is ~8-14 fold and P.1 is ~2.6-5 fold more resistant to neutralization by convalescent plasma and mRNA vaccinee sera (63)(64)(65)(66)(67)(68).…”

mentioning

confidence: 99%

Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants

Yuan

Huang

Lee

et al. 2021

Science

333

335

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Neutralizing antibodies (nAbs) elicited against the receptor-binding site (RBS) of the spike protein of wild-type SARS-CoV-2 are generally less effective against recent variants of concern. RBS residues E484, K417 and N501 are mutated in variants first described in South Africa (B.1.351) and Brazil (P.1). We analyzed their effects on ACE2 binding and K417N and E484K mutations on nAbs isolated from COVID-19 patients. Binding and neutralization of the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2), which can both bind the RBS in alternate binding modes, are abrogated by K417N, E484K, or both. These effects can be structurally explained by their extensive interactions with RBS nAbs. However, nAbs to the more conserved, cross-neutralizing CR3022 and S309 sites were largely unaffected. The results have implications for next-generation vaccines and antibody therapies.

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Antibodies with potent and broad neutralizing activity against antigenically diverse and highly transmissible SARS-CoV-2 variants

Cited by 23 publications

References 29 publications

Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies

Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies

Mutational escape from the polyclonal antibody response to SARS-CoV-2 infection is largely shaped by a single class of antibodies

Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants

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