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mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants.
Nature. 2021 04; 592(7855):616-622.Nat

Abstract

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.

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Authors+Show Affiliations

Wang Z
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Schmidt F
Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
Weisblum Y
Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
Muecksch F
Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
Barnes CO
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Finkin S
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Schaefer-Babajew D
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Cipolla M
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Gaebler C
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Lieberman JA
Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Oliveira TY
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Yang Z
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Abernathy ME
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Huey-Tubman KE
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Hurley A
Hospital Program Direction, The Rockefeller University, New York, NY, USA.
Turroja M
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
West KA
Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Gordon K
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Millard KG
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Ramos V
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Da Silva J
Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
Xu J
Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Colbert RA
Pediatric Translational Research Branch and Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Patel R
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Dizon J
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Unson-O'Brien C
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Shimeliovich I
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Gazumyan A
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Caskey M
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Bjorkman PJ
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. bjorkman@caltech.edu.
Casellas R
Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA. rafael.casellas@nih.gov. The NIH Regulome Project, National Institutes of Health, Bethesda, MD, USA. rafael.casellas@nih.gov.
Hatziioannou T
Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA. thatziio@rockefeller.edu.
Bieniasz PD
Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA. pbieniasz@rockefeller.edu. Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. pbieniasz@rockefeller.edu.
Nussenzweig MC
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA. nussen@rockefeller.edu. Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. nussen@rockefeller.edu.

MeSH

2019-nCoV Vaccine mRNA-1273AdultAgedAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralB-LymphocytesBNT162 VaccineCOVID-19COVID-19 VaccinesCryoelectron MicroscopyEpitopes, B-LymphocyteFemaleHumansImmunization, SecondaryImmunoglobulin GImmunoglobulin MImmunologic MemoryMaleMiddle AgedModels, MolecularMutationNeutralization TestsSARS-CoV-2Spike Glycoprotein, CoronavirusVaccines, Synthetic

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33567448

Citation

Wang, Zijun, et al. "MRNA Vaccine-elicited Antibodies to SARS-CoV-2 and Circulating Variants." Nature, vol. 592, no. 7855, 2021, pp. 616-622.
Wang Z, Schmidt F, Weisblum Y, et al. MRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature. 2021;592(7855):616-622.
Wang, Z., Schmidt, F., Weisblum, Y., Muecksch, F., Barnes, C. O., Finkin, S., Schaefer-Babajew, D., Cipolla, M., Gaebler, C., Lieberman, J. A., Oliveira, T. Y., Yang, Z., Abernathy, M. E., Huey-Tubman, K. E., Hurley, A., Turroja, M., West, K. A., Gordon, K., Millard, K. G., ... Nussenzweig, M. C. (2021). MRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature, 592(7855), 616-622. https://doi.org/10.1038/s41586-021-03324-6
Wang Z, et al. MRNA Vaccine-elicited Antibodies to SARS-CoV-2 and Circulating Variants. Nature. 2021;592(7855):616-622. PubMed PMID: 33567448.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. AU - Wang,Zijun, AU - Schmidt,Fabian, AU - Weisblum,Yiska, AU - Muecksch,Frauke, AU - Barnes,Christopher O, AU - Finkin,Shlomo, AU - Schaefer-Babajew,Dennis, AU - Cipolla,Melissa, AU - Gaebler,Christian, AU - Lieberman,Jenna A, AU - Oliveira,Thiago Y, AU - Yang,Zhi, AU - Abernathy,Morgan E, AU - Huey-Tubman,Kathryn E, AU - Hurley,Arlene, AU - Turroja,Martina, AU - West,Kamille A, AU - Gordon,Kristie, AU - Millard,Katrina G, AU - Ramos,Victor, AU - Da Silva,Justin, AU - Xu,Jianliang, AU - Colbert,Robert A, AU - Patel,Roshni, AU - Dizon,Juan, AU - Unson-O'Brien,Cecille, AU - Shimeliovich,Irina, AU - Gazumyan,Anna, AU - Caskey,Marina, AU - Bjorkman,Pamela J, AU - Casellas,Rafael, AU - Hatziioannou,Theodora, AU - Bieniasz,Paul D, AU - Nussenzweig,Michel C, Y1 - 2021/02/10/ PY - 2021/01/15/received PY - 2021/02/03/accepted PY - 2021/2/11/pubmed PY - 2021/4/29/medline PY - 2021/2/10/entrez SP - 616 EP - 622 JF - Nature JO - Nature VL - 592 IS - 7855 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/33567448/mRNA_vaccine_elicited_antibodies_to_SARS_CoV_2_and_circulating_variants_ DB - PRIME DP - Unbound Medicine ER -