Seasonal Betacoronavirus Antibodies’ Expansion Post-BNT161b2 Vaccination Associates with Reduced SARS-CoV-2 VoC Neutralization

  1. Stefania Dispinseri
  2. Ilaria Marzinotto
  3. Cristina Brigatti
  4. Maria Franca Pirillo
  5. Monica Tolazzi
  6. Elena Bazzigaluppi
  7. Andrea Canitano
  8. Martina Borghi
  9. Alessandra Gallinaro
  10. Roberta Caccia
  11. Riccardo Vercesi
  12. Paul F. McKay
  13. Fabio Ciceri
  14. Lorenzo Piemonti
  15. Donatella Negri
  16. Paola Cinque
  17. Andrea Cara
  18. Gabriella Scarlatti
  19. Vito Lampasona

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Abstract

SARS-CoV-2 vaccination is known to induce antibodies that recognize also variants of concerns (VoCs) of the virus. However, epidemiological and laboratory evidences indicate that these antibodies have a reduced neutralization ability against VoCs. We studied binding and neutralizing antibodies against the Spike protein domains and subunits of the Wuhan-Hu-1 virus and its alpha, beta, delta VoCs and of seasonal betacoronaviruses (HKU1 and OC43) in a cohort of 31 health care workers prospectively followed post-vaccination with BNT162b2-Comirnaty. The study of sequential samples collected up to 64 days post-vaccination showed that serological assays measuring IgG against Wuhan-Hu-1 antigens were a poor proxy for VoC neutralization. In addition, in subjects who had asymptomatic or mild COVID-19 prior to vaccination, the loss of nAbs following disease could be rapid and accompanied by post-vaccination antibody levels similar to those of naïve vaccinees. Interestingly, in health care workers naïve for SARS-CoV-2 infection, vaccination induced a rapid and transient reactivation of pre-existing seasonal coronaviruses IgG responses that was associated with a subsequent reduced ability to neutralize alpha and beta VoCs.

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  1. Version published to 10.1007/s10875-021-01190-5
  2. ScreenIT

    SciScore for 10.1101/2021.08.15.21262000: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Written informed consent was obtained from all individual participants included in the study.
    IRB: The study subjects belonged to the IRCCS Ospedale San Raffaele COVID-19 cohort study COVID-BioB (registered as ClinicalTrialsgov-NCT04318366) and approved by the IRCCS Ospedale San Raffaele Ethics Review Board (protocol 68/INT/2020) and the COVID-BioB related immunological sub-studies “Role of the immune response in the infection with SARS-CoV-2 and in the pathogenesis of COVID-19” (protocol number 34/int/2020).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    A confirmed infection case was defined as a SARS-CoV-2 positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR) from a nasopharyngeal swab and/or COVID-19 symptoms and/or a serologic evidence of antibody to SARS-CoV-2.
    SARS-CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Briefly, 293T Lenti-X cells (3.5×106 cells) were seeded on 10 cm Petri dishes (Corning Incorporated - Life Sciences, Oneonta, NY, USA) and transiently transfected with plasmids pGAE-LucW, pADSIV3+ and pseudotyping plasmid (pSpike-C3, pSpike-UKC3, pSpike-SAC3) using the JetPrime transfection kit (
    293T
    suggested: None
    Briefly, heat-inactivated serum serial 3-fold dilutions starting from the 1/40 dilution were incubated in duplicate with the LV-Luc for 30 min at 37°C in 96-well plates, and thereafter added to VeroE6 cells at a density of 20.000 cells/well.
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Recombinant DNA
    SentencesResources
    For construction of pSpike-UKC3 and pSpike-SAC3 plasmids, expressing the variant Spike ORFs with a 21 amino acid deletion at the cytoplasmic tail, a NheI/AvaI fragment of DNA was removed from Alpha (B.1.1.7 pSpike-UK) and Beta (B.1.351 pSpike-SA) plasmids and inserted into the corresponding restriction sites of pSpike-C3 plasmid, to obtain pSpike-UKC3 and pSpike-SAC3 plasmids.
    pSpike-UK
    suggested: None
    pSpike-SA
    suggested: None
    pSpike-UKC3
    suggested: None
    pSpike-SAC3
    suggested: None
    Briefly, 293T Lenti-X cells (3.5×106 cells) were seeded on 10 cm Petri dishes (Corning Incorporated - Life Sciences, Oneonta, NY, USA) and transiently transfected with plasmids pGAE-LucW, pADSIV3+ and pseudotyping plasmid (pSpike-C3, pSpike-UKC3, pSpike-SAC3) using the JetPrime transfection kit (
    pGAE-LucW
    suggested: None
    pADSIV3+
    suggested: None
    pSpike-C3
    suggested: None

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04318366RecruitingCOVID-19 Patients Characterization, Biobank, Treatment Respo…

    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.

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  3. Version published to 10.1101/2021.08.15.21262000v1 on medRxiv