A human coronavirus evolves antigenically to escape antibody immunity

Eguia, Rachel; Crawford, Katharine H.D.; Stevens-Ayers, Terry; Kelnhofer-Millevolte, Laurel; Greninger, Alexander L.; Englund, Janet A.; Boeckh, Michael; Bloom, Jesse D.

doi:10.1101/2020.12.17.423313

Cited by 65 publications

(66 citation statements)

References 94 publications

(145 reference statements)

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“…We speculate that these mutations emerged in response to immune selection in individuals with non-sterilizing immunity. What the long-term effect of accumulation of mutations on the SARS-CoV-2 pandemic will be is not known, but the common cold coronavirus HCoV-229E evolves antigenic variants that are comparatively resistant to the older sera but remain sensitive to contemporaneous sera 50 . Thus, it is possible that these mutations and others that emerge in individuals with suboptimal or waning immunity will erode the effectiveness of natural and vaccine elicited immunity.…”

Section: Discussionmentioning

confidence: 99%

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

Wang

Schmidt

Weisblum

et al. 2021

Preprint

280

313

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To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease 2019 (COVID-19) including two novel mRNA-based vaccines1,2. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known3–6. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers3,5,6. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection7,8. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

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Section: Discussionmentioning

confidence: 99%

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

Wang

Schmidt

Weisblum

et al. 2021

Preprint

280

313

View full text Add to dashboard Cite

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“…More broadly, our maps suggest that it may be advisable to more systematically consider possible escape mutations when devising antibodies for clinical use against SARS-CoV-2. It is now clear that human coronaviruses undergo antigenic evolution in response to immune pressure [26,27], and we and others have begun to map out the key sites in the RBD that are targeted by human antibody immunity [19,28–30]. The recent rise in frequency of mutations at site E484 suggests that this immunity may be beginning to drive antigenic variation within immunodominant positions in the RBD.…”

Section: Discussionmentioning

confidence: 99%

Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016

Starr

Greaney

Dingens

et al. 2021

Preprint

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119

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Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for COVID-19. However, ongoing evolution of SARS-CoV-2 can render monoclonal antibodies ineffective. Here we completely map all mutations to the SARS-CoV-2 spike receptor binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escape LY-CoV016). Additionally, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts should diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to antigenic evolution of SARS-CoV-2.

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“…Neutralizing antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike are associated with protection against infection in both humans (Addetia et al, 2020;Lumley et al, 2020) and animals (Alsoussi et al, 2020;Walls et al, 2020;Zost et al, 2020a). However, other human coronaviruses undergo antigenic evolution that erodes neutralizing antibody immunity (Eguia et al, 2020). This antigenic evolution is driven by positive selection for mutations in the viral spike, particularly in regions involved in receptor binding (Kistler and Bedford, 2021;Wong et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies

Greaney

Loes

Crawford

et al. 2021

Cell Host & Microbe

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1,098

1,190

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The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent plasma antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal the impact of these mutations on antibody binding varies substantially both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor binding motif. The most important site is E484, where neutralization by some plasma is reduced >10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.

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A human coronavirus evolves antigenically to escape antibody immunity

Cited by 65 publications

References 94 publications

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016

Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies

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