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Primary, Recall, and Decay Kinetics of SARS-CoV-2 Vaccine Antibody Responses

  • 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
  • , and 
  • 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
Cite this: ACS Nano 2021, 15, 7, 11180–11191
Publication Date (Web):June 23, 2021
https://doi.org/10.1021/acsnano.1c03972
Copyright © 2021 American Chemical Society

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    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.

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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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