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Primary, Recall, and Decay Kinetics of SARS-CoV-2 Vaccine Antibody Responses
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    Primary, Recall, and Decay Kinetics of SARS-CoV-2 Vaccine Antibody Responses
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    • F. Javier Ibarrondo
      F. Javier Ibarrondo
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
    • Christian Hofmann
      Christian Hofmann
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
    • Jennifer A. Fulcher
      Jennifer A. Fulcher
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
    • David Goodman-Meza
      David Goodman-Meza
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
    • William Mu
      William Mu
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
      More by William Mu
    • Mary Ann Hausner
      Mary Ann Hausner
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
    • Ayub Ali
      Ayub Ali
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
      More by Ayub Ali
    • Arumugam Balamurugan
      Arumugam Balamurugan
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
    • Ellie Taus
      Ellie Taus
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
      More by Ellie Taus
    • Julie Elliott
      Julie Elliott
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
    • Paul Krogstad
      Paul Krogstad
      Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
    • Nicole H. Tobin
      Nicole H. Tobin
      Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
    • Kathie G. Ferbas
      Kathie G. Ferbas
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
    • Scott G. Kitchen
      Scott G. Kitchen
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
    • Grace M. Aldrovandi
      Grace M. Aldrovandi
      Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
    • Anne W. Rimoin
      Anne W. Rimoin
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
      Fielding School of Public Health, University of California Los Angeles, Los Angeles, California 90095, United States
    • Otto O. Yang*
      Otto O. Yang
      Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
      Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
      *Phone: 310-794-9491. Fax: 310-983-1067. Email: [email protected]
      More by Otto O. Yang
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    ACS Nano

    Cite this: ACS Nano 2021, 15, 7, 11180–11191
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    https://doi.org/10.1021/acsnano.1c03972
    Published June 23, 2021
    Copyright © 2021 American Chemical Society

    Abstract

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    Studies of two SARS-CoV-2 mRNA vaccines suggested that they yield ∼95% protection from symptomatic infection at least short-term, but important clinical questions remain. It is unclear how vaccine-induced antibody levels quantitatively compare to the wide spectrum induced by natural SARS-CoV-2 infection. Vaccine response kinetics and magnitudes in persons with prior COVID-19 compared to virus-naı̈ve persons are not well-defined. The relative stability of vaccine-induced versus infection-induced antibody levels is unclear. We addressed these issues with longitudinal assessments of vaccinees with and without prior SARS-CoV-2 infection using quantitative enzyme-linked immunosorbent assay (ELISA) of anti-RBD antibodies. SARS-CoV-2-naı̈ve individuals achieved levels similar to mild natural infection after the first vaccination; a second dose generated levels approaching severe natural infection. In persons with prior COVID-19, one dose boosted levels to the high end of severe natural infection even in those who never had robust responses from infection, increasing no further after the second dose. Antiviral neutralizing assessments using a spike-pseudovirus assay revealed that virus-naı̈ve vaccinees did not develop physiologic neutralizing potency until the second dose, while previously infected persons exhibited maximal neutralization after one dose. Finally, antibodies from vaccination waned similarly to natural infection, resulting in an average of ∼90% loss within 90 days. In summary, our findings suggest that two doses are important for quantity and quality of humoral immunity in SARS-CoV-2-naı̈ve persons, while a single dose has maximal effects in those with past infection. Antibodies from vaccination wane with kinetics very similar to that seen after mild natural infection; booster vaccinations will likely be required.

    Copyright © 2021 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.1c03972.

    • Supplemental Table S1, peak antibody levels after vaccination Figure 2 (XLSX)

    • Supplemental Table S2, longitudinal antibody levels in persons with prior SARS-CoV-2 infection and vaccination (XLSX)

    • Supplemental Table S3, vaccination antibody levels used for modeling Table 1 (XLSX)

    • Supplemental Table S4, serum neutralizing activity after vaccination (XLSX)

    • Supplemental Table S5, longitudinal antibody levels after vaccination and decay slopes (XLSX)

    • Supplemental Figure S1, evaluation of serum neutralizing activity (PDF)

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    ACS Nano

    Cite this: ACS Nano 2021, 15, 7, 11180–11191
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    https://doi.org/10.1021/acsnano.1c03972
    Published June 23, 2021
    Copyright © 2021 American Chemical Society

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