Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection

Greaney, Allison J; Loes, Andrea N; Gentles, Lauren E.; Crawford, Katharine H.D.; Starr, Tyler N; Malone, Keara D.; Chu, Helen Y.; Bloom, Jesse D.

doi:10.1126/scitranslmed.abi9915

Cited by 225 publications

(252 citation statements)

References 66 publications

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“…A similarly unequal immunodominance of different epitopes has also been described for other viral antigens, such as influenza hemagglutinin 41,42 . However, the immunodominance of different epitopes can vary depending on the antigen formulation and delivery 41 , and there is preliminary evidence that some vaccines could elicit antibody responses to SARS-CoV-2 with immunodominance hierarchies that are less skewed than those elicited by infection 10,16,43,44 .…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Interestingly, mRNA vaccines induce disproportionately more anti-RBD antibodies compared to natural infection, which tend to target other portions of the spike protein [ 143 ]. Vaccine-induced antibodies also target a broader range of areas on the RBD, meaning those antibodies are better able to respond potently against new variants even when they carry mutations in the RBD [ 143 ]. Therefore, while the emergence of new SARS-CoV-2 variants remains a threat to herd immunity, current vaccines remain effective and provide superior protection to natural disease.…”

Section: Implications Of Waning Antibodies On Covid-19mentioning

confidence: 99%

Waning antibody responses in COVID-19: what can we learn from the analysis of other coronaviruses?

2021

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Objectives The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due to the continuing surge in incidence and mortality globally, determining whether protective, long-term immunity develops after initial infection or vaccination has become critical. Methods/Results In this narrative review, we evaluate the latest understanding of antibody-mediated immunity to SARS-CoV-2 and to other coronaviruses (SARS-CoV, Middle East respiratory syndrome coronavirus and the four endemic human coronaviruses) in order to predict the consequences of antibody waning on long-term immunity against SARS-CoV-2. We summarise their antibody dynamics, including the potential effects of cross-reactivity and antibody waning on vaccination and other public health strategies. At present, based on our comparison with other coronaviruses we estimate that natural antibody-mediated protection for SARS-CoV-2 is likely to last for 1–2 years and therefore, if vaccine-induced antibodies follow a similar course, booster doses may be required. However, other factors such as memory B- and T-cells and new viral strains will also affect the duration of both natural and vaccine-mediated immunity. Conclusion Overall, antibody titres required for protection are yet to be established and inaccuracies of serological methods may be affecting this. We expect that with standardisation of serological testing and studies with longer follow-up, the implications of antibody waning will become clearer.

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“…S3). The RBD is the main target of serum neutralizing activity in convalescent and vaccinated individuals and comprises several antigenic sites recognized by neutralizing Abs with a range of neutralization potencies and breadth (15)(16)(17)(18)(49)(50)(51). The B.1.617.1 S and B.1.617.2 S structures resolve the complete RBD and provide high-resolution blueprints of the residue substitutions found in these two variants (Fig 2C-D).…”

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confidence: 99%

Molecular basis of immune evasion by the delta and kappa SARS-CoV-2 variants

McCallum

Walls

Sprouse

et al. 2021

Preprint

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Worldwide SARS-CoV-2 transmission leads to the recurrent emergence of variants, such as the recently described B.1.617.1 (kappa), B.1.617.2 (delta) and B.1.617.2+ (delta+). The B.1.617.2 (delta) variant of concern is causing a new wave of infections in many countries, mostly affecting unvaccinated individuals, and has become globally dominant. We show that these variants dampen the in vitro potency of vaccine-elicited serum neutralizing antibodies and provide a structural framework for describing the impact of individual mutations on immune evasion. Mutations in the B.1.617.1 (kappa) and B.1.617.2 (delta) spike glycoproteins abrogate recognition by several monoclonal antibodies via alteration of key antigenic sites, including an unexpected remodeling of the B.1.617.2 (delta) N-terminal domain. The binding affinity of the B.1.617.1 (kappa) and B.1.617.2 (delta) receptor-binding domain for ACE2 is comparable to the ancestral virus whereas B.1.617.2+ (delta+) exhibits markedly reduced affinity. We describe a previously uncharacterized class of N-terminal domain-directed human neutralizing monoclonal antibodies cross-reacting with several variants of concern, revealing a possible target for vaccine development.

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Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection

Cited by 225 publications

References 66 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

Waning antibody responses in COVID-19: what can we learn from the analysis of other coronaviruses?

Molecular basis of immune evasion by the delta and kappa SARS-CoV-2 variants

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