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

By Zijun Wang, F. Schmidt, Y. Weisblum, Frauke Muecksch, C. Barnes, Shlomo Finkin, Dennis J. Schaefer-Babajew, M. Cipolla, C. Gaebler, J. Lieberman and 24 more. Nature, 2021

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Here we report on the antibody and memory B cell responses of a cohort of 20 volunteers who received the Moderna (mRNA-1273) or Pfizer–BioNTech (BNT162b2) vaccine against SARS-CoV-21–4. Eight weeks after the second injection of vaccine, volunteers showed high levels of IgM and IgG anti-SARS-CoV-2 spike protein (S) and receptor-binding-domain (RBD) binding titre. Moreover, the plasma neutralizing activity and relative numbers of RBD-specific memory B cells of vaccinated volunteers were equivalent to those of individuals who had recovered from natural infection5,6. However, activity against SARS-CoV-2 variants that encode E484K-, N501Y- or K417N/E484K/N501-mutant S was reduced by a small—but significant—margin. The monoclonal antibodies elicited by the vaccines potently neutralize SARS-CoV-2, and target a number of different RBD epitopes in common with monoclonal antibodies isolated from infected donors5–8. However, neutralization by 14 of the 17 most-potent monoclonal antibodies that we tested was reduced or abolished by the K417N, E484K or N501Y mutation. Notably, these mutations were selected when we cultured recombinant vesicular stomatitis virus expressing SARS-CoV-2 S in the presence of the monoclonal antibodies elicited by the vaccines. Together, these 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 a potential loss of clinical efficacy. The Moderna (mRNA-1273) and Pfizer–BioNTech (BNT162b2) vaccines elicit anti-RBD antibodies similar to those elicited through natural infection with SARS-CoV-2, but their potent neutralizing activity was reduced or abolished by new viral variants of concern.

Subfields: Animal Science and Zoology, Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/84d324c78bb9a8de3802c4572eec381e9002ca30

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In Immunology

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Citations in the corpus

• SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies (2021, positive): “1 variants (E484K +N501Y) wasmoderately reduced (Liu et al., 2021; Wang et al., 2021; Xie et al., 2021), again in keeping with our findings.”
• Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil (2021, background): “Moreover, E484K is associated with reduced antibody neutralisation (6, 56-58).”
• mRNA Vaccines in the COVID-19 Pandemic and Beyond. (2021, result): “In early studies, both the neutralizing antibody responses (33) and efficacy in preventing symptomatic COVID-19 within 2 months of follow-up (5, 6) were indistinguishable between the Moderna and Pfizer/BioNTech vaccines, made using similar nucleoside-modified mRNA-LNP technologies.”
• The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic (2021, positive): “Another 15 mutations are found in the RBD (Figure 1C-E), of which G339D, S371L, S373P and S375F are unique, and several were previously shown to modulate ACE2 binding and/or antibody evasion (Harvey et al., 2021b; Li et al., 2021b; Liu et al., 2021; Wang et al., 2021; Wheatley et al., 2021).”
• Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial. (2021, background): “During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.”