Symptomatology during previous SARS-CoV-2 infection and serostatus before vaccination influence the immunogenicity of BNT162b2 COVID-19 mRNA vaccine

  1. Sabryna Nantel
  2. Benoîte Bourdin
  3. Kelsey Adams
  4. Julie Carbonneau
  5. Henintsoa Rabezanahary
  6. Marie-Ève Hamelin
  7. Deirdre McCormack
  8. Patrice Savard
  9. Yves Longtin
  10. Matthew P. Cheng
  11. Gaston De Serres
  12. Jacques Corbeil
  13. Vladimir Gilca
  14. Mariana Baz
  15. Guy Boivin
  16. Caroline Quach
  17. Hélène Decaluwe

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Abstract

Public health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. This study presents detailed immunological evidence to clarify the requirements for one- or two-dose primary vaccination series for naturally primed individuals. The main objective was to evaluate the immune response to COVID-19 mRNA vaccination to establish the most appropriate vaccination regimen to induce robust immune responses in individuals with prior SARS-CoV-2 infection. The main outcome measure was a functional immunity score (zero to three) before and after vaccination, based on anti-RBD IgG levels, serum capacity to neutralize live virus and IFN-γ secretion capacity in response to SARS-CoV-2 peptide pools. One point was attributed for each of these three functional assays with response above the positivity threshold. The immunity score was compared based on subjects’ symptoms at diagnosis and/or serostatus prior to vaccination. None of the naïve participants (n=14) showed a maximal immunity score of three following one dose of vaccine compared to 84% of the previously infected participants (n=55). All recovered individuals who did not have an immunity score of three were seronegative prior to vaccination, and 67% had not reported symptoms resulting from their initial infection. Following one dose of vaccine, their immune responses were comparable to naïve individuals, with significantly weaker responses than individuals who were symptomatic during infection. These results indicate that the absence of symptoms during initial infection and negative serostatus prior to vaccination predict the strength of immune responses to COVID-19 mRNA vaccine. Altogether, these findings highlight the importance of administering the complete two-dose primary regimen and following boosters of mRNA vaccines to individuals who experienced asymptomatic SARS-CoV-2 infection.

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  1. Version published to 10.3389/fimmu.2022.930252
  2. ScreenIT

    SciScore for 10.1101/2022.03.29.22272714: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Sample Collection and Processing: Blood samples were collected into serum separation tubes (SST(tm), BD) and acid–citrate–dextrose tubes (ACD, BD).
    IRB: Significance was set as *p <.05; **p <.01; ***p <.001; ****p <.0001. Ethics: RECOVER protocols were approved by the Research Ethics Board (REB) at the CHU Sainte-Justine (CHUSJ) under study MP-21-2021-3035 and in each of the five participating centers in the Province of Québec.
    Consent: Written informed consent was obtained from all participants during the recruitment period, and ongoing consent was reviewed at each subsequent visit.
    Sex as a biological variablenot detected.
    RandomizationParticipants who were symptomatic during infection (n=26) were randomly selected from the rest of the RECOVER cohort based on their serostatus at enrollment after being matched with participants from the asymptomatic group for sex, age, time since infection and time between infection and vaccination.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Laboratory.23 Absence of previous infection to SARS-CoV-2 was confirmed in the naïve cohort by performing an ELISA detecting specific IgG antibodies for the Nucleoprotein (anti-N) of SARS-CoV-2 and the anti-RBD ELISA before vaccination.
    anti-N
    suggested: None
    anti-RBD
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The residual infectivity of those mixtures was assessed in quadruplicate wells of African green monkey kidney E6 cell line (Vero ATCC® CRL-1586™)
    Vero
    suggested: ATCC Cat# CRL-1586, RRID:CVCL_0574)
    Software and Algorithms
    SentencesResources
    FlowJo software, version 10.7.1, was used to perform all data analysis.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistics: All statistical tests were performed using Prism 9, version 9.2.0 (2021 GraphPad Software, LLC) and data were displayed as mean ± SEM. Wilcoxon-Mann-Whitney or Kruskal-Wallis tests were used to evaluate statistical significance between groups for variables that did not follow a normal distribution.
    GraphPad
    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:
    Limitations: Results of this study were obtained from a cohort of primarily middle-aged Caucasian females infected with SARS-CoV-2 eight months before vaccination. It remains to be evaluated if a shorter time between infection and vaccination will lead to similar results. Our study is also limited by a relatively small sample size of participants who did not experience symptoms during their initial infection. It will be essential to validate our findings in a larger population of subjects, as immune responses to SARS-CoV-2 are known to be highly heterogeneous. Furthermore, the protection induced by booster doses against VOCs in previously infected individuals remains to be evaluated. This study did not assess the impact of other approved adenovirus or mRNA vaccines against SARS-CoV-249,50, as primary series or boosters, as well as natural infection with emerging SARS-CoV-2 VOCs, as most of the cohort was infected at the beginning of 2020.51 Finally, the immunity score may underestimate the quality of the immune memory generated in recovered individuals since it is limited to three of the most standardized assays to interrogate immune response to SARS-CoV-2. Detailed functional, transcriptomic and repertoire analyses will be essential to fully grasp the immune memory differences between individuals who experienced symptoms or not following infection.

    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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  3. Version published to 10.1101/2022.03.29.22272714 on medRxiv