Single-dose SARS-CoV-2 vaccine in a prospective cohort of COVID-19 patients

  1. Marit J. van Gils
  2. Hugo D. van Willigen
  3. Elke Wynberg
  4. Alvin X. Han
  5. Karlijn van der Straten
  6. Anouk Verveen
  7. Romy Lebbink
  8. Maartje Dijkstra
  9. Judith A. Burger
  10. Melissa Oomen
  11. Khadija Tejjani
  12. Joey H. Bouhuijs
  13. Brent Appelman
  14. Ayesha H.A. Lavell
  15. Meliawati Poniman
  16. Tom G. Caniels
  17. Ilja Bontjer
  18. Lonneke A. van Vught
  19. Alexander P.J. Vlaar
  20. Jonne J. Sikkens
  21. Marije K. Bomers
  22. Rogier W. Sanders
  23. Neeltje A. Kootstra
  24. Colin Russell
  25. Maria Prins
  26. Godelieve J. de Bree
  27. Menno D. de Jong
  28. RECoVERED Study Group

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Abstract

Background

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose sparing strategies, particularly single vaccine dosing of individuals with prior SARS-CoV-2 infection.

Methods

We evaluated SARS-CoV-2 specific antibody responses following a single-dose of BNT162b2 (Pfizer-BioNTech) mRNA vaccine in 155 previously SARS-CoV-2-infected individuals participating in a population-based prospective cohort study of COVID-19 patients.

Participants varied widely in age, comorbidities, COVID-19 severity and time since infection, ranging from 1 to 15 months. Serum antibody titers were determined at time of vaccination and one week after vaccination. Responses were compared to those in SARS-CoV-2-naive health care workers after two BNT162b2 mRNA vaccine doses.

Results

Within one week of vaccination, IgG antibody levels to virus spike and RBD proteins increased 27 to 29-fold and neutralizing antibody titers increased 12-fold, exceeding titers of fully vaccinated SARS-CoV-2-naive controls (95% credible interval (CrI): 0.56 to 0.67 v. control 95% CrI: −0.16 to −0.02). Pre-vaccination neutralizing antibody titers had the largest positive mean effect size on titers following vaccination (95% CrI (0.16 to 0.45)). COVID-19 severity, the presence of comorbidities and the time interval between infection and vaccination had no discernible impact on vaccine response.

Conclusion

A single dose of BNT162b2 mRNA vaccine up to 15 months after SARS-CoV-2 infection provides neutralizing titers exceeding two vaccine doses in previously uninfected individuals. These findings support wide implementation of a single-dose mRNA vaccine strategy after prior SARS-CoV-2 infection.

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  1. ScreenIT

    SciScore for 10.1101/2021.05.25.21257797: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The RECoVERED study, including the vaccine substudy, and the S3 study were approved by the medical ethical review board of the Amsterdam University Medical Centers (NL73759.018.20 and NL73478.029.20, respectively).
    Consent: All participants provided written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 binding IgG antibody levels: Levels of Immunoglobulin G (IgG) binding to SARS-CoV-2 receptor-binding domain (RBD), nucleocapsid (N) and spike (S) proteins of wild type virus (Wu-1) and variants of concern (B.1.1.7, B.1.351 and P.1), as well as to control proteins tetanus toxoid, respiratory syncytial virus glycoprotein (RSV-G) and influenza A/H1N1pdm09 virus HA protein, were determined using a custom luminex assay as described previously.
    SARS-CoV-2 binding IgG
    suggested: None
    SARS-CoV-2 receptor-binding domain ( RBD) , nucleocapsid ( N )
    suggested: None
    Statistical analysis: A Bayesian hierarchical generalization of the one-way ANOVA model was used to compare control, pre- and post-vaccination neutralizing and IgG antibody binding titers.
    IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    14 In short, proteins were produced in HEK293F cells (Invitrogen) and purified from the cell culture supernatant using affinity chromatography with NiNTA agarose beads (Qiagen).
    HEK293F
    suggested: RRID:CVCL_6642)
    Software and Algorithms
    SentencesResources
    The 50% inhibitory dilution (ID50) titers were determined as the serum dilution at which infectivity was inhibited by 50% using a non-linear regression curve fit (GraphPad Prism software version 8.3).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are several limitations of our study. As only symptomatic COVID-19 patients were followed we were unable to study vaccine responses after previous asymptomatic SARS-CoV-2 infection. However, an earlier study in HCW has observed no differences in antibody responses to a mRNA vaccine between individuals with prior asymptomatic and symptomatic SARS-CoV-2 infections.10 Furthermore, the SARS-CoV-2 naive HCW controls were not matched with the previously infected cohort participants for potentially relevant factors such as age, sex or the presence of comorbidities. However, given that antibody responses in the healthier and younger HCW controls were lower, combined with our finding that age is inversely correlated with antibody vaccine response, the observed difference in vaccine response might even have been more pronounced if controls were matched. Finally, participants with severe COVID-19 were overrepresented in the subgroup with >12 months interval between infection and vaccination, but fold increases in neutralization were very similar for all time interval subgroups, independent of disease severity. Longer follow up will determine the longevity of the immune response and protective efficacy after single dosing in previously infected individuals. In addition, while similar antibody boost responses would be anticipated for other SARS-Co V-2 vaccines, this needs to be confirmed in future studies, especially for non-mRNA vaccines. In the meantime, the findings of this study...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2021.05.25.21257797v1 on medRxiv