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

Abstract

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) vaccines1–4. Eight 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 titers. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection5,6. 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. Vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors5–8. 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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Correspondence to Pamela J. Bjorkman or Rafael Casellas or Theodora Hatziioannou or Paul D. Bieniasz or Michel C. Nussenzweig.

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Reporting Summary

Supplementary Table 1

Individual vaccine characteristics.

Supplementary Table 2

Neutralization of WT/KEN pseudovirus by convalescent plasma.

Supplementary Table 3

Antibody sequences from vaccines.

Supplementary Table 4

CDR3 alignment of highly identical clonal sequences.

Supplementary Table 5

Sequences, half maximal effective concentrations (EC50s) and inhibitory concentrations (IC50s) of the cloned monoclonal antibodies.

Supplementary Table 6

Neutralization activity of mAbs against mutant SARS-CoV-2 pseudoviruses.

Supplementary Table 7

Cryo-EM data collection and processing statistics.

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Wang, Z., Schmidt, F., Weisblum, Y. et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature (2021). https://doi.org/10.1038/s41586-021-03324-6

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