Can Individuals with Suboptimal Antibody Responses to Conventional Antiviral Vaccines Acquire Adequate Antibodies from SARS-CoV-2 mRNA Vaccination?

  1. Wataru Ogura
  2. Kouki Ohtsuka
  3. Sachiko Matsuura
  4. Takahiro Okuyama
  5. Satsuki Matsushima
  6. Satoko Yamasaki
  7. Hiroyuki Miyagi
  8. Kumiko Sekiguchi
  9. Hiroaki Ohnishi
  10. Takashi Watanabe

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Abstract

In Japan, healthcare workers (HCWs) are vaccinated against measles, rubella, chickenpox, mumps, and hepatitis B to prevent nosocomial infection; however, some do not produce sufficient antibodies (“suboptimal responders”). This study compared immune responses to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 mRNA) vaccine among HCWs with normal and suboptimal responses to conventional vaccines. In this prospective cohort study, 50 HCWs received two doses of BNT162b2 mRNA vaccine 3 weeks apart. SARS-CoV-2 anti-spike antibodies were measured 11 times, starting before the first vaccination and ending 5 months after the second vaccination. Antibody titers of four suboptimal and 46 normal responders were compared. SARS-CoV-2 neutralizing antibody activity was measured twice in suboptimal responders, 1 week/1 month and 5 months after the second vaccination. The SARS-CoV-2 anti-spike antibody was detectable in the samples from suboptimal and normal responders at each timepoint after vaccination. Suboptimal responders exhibited SARS-CoV-2 neutralizing antibody activity 1 week/1 month as well as 5 months after the second vaccination; however, activity was slightly reduced at 5 months. Our findings show that suboptimal responders do acquire adequate SARS-CoV-2 anti-spike and SARS-CoV-2 neutralizing antibodies from vaccination to prevent SARS-CoV-2. SARS-CoV-2 mRNA vaccines should thus be recommended for both normal and suboptimal responders to conventional vaccines.

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  1. Version published to 10.3390/v14050956
  2. Version published to 10.1101/2021.12.26.21268358v4 on medRxiv
  3. Version published to 10.1101/2021.12.26.21268358v3 on medRxiv
  4. Version published to 10.1101/2021.12.26.21268358v2 on medRxiv
  5. ScreenIT

    SciScore for 10.1101/2021.12.26.21268358: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was conducted with the approval of the Ethics Committee of Kyorin University School of Medicine (Number R02-041; May 19, 2020).
    Consent: Informed consent was obtained from all study participants.
    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 anti-spike antibody assay: SARS-CoV-2 anti-spike antibody measurements were performed on serum obtained from centrifuged peripheral blood using the Elecsys Anti-SARS-CoV-2 S RUO (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) on a Cobas 6000 (Roche Diagnostics) analyzer via the double-antigen sandwich enzyme-linked immunoassay method [15].
    SARS-CoV-2
    suggested: None
    anti-spike
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    After incubation, 100 μL of the mixture was added to the Vero cells in a 96-well plate.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    Percent neutralization was calculated using GraphPad Prism 8.0.2 software (GraphPad Software, California, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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:
    This study has some limitations. The number of participants was limited, and all participants were HCWs vaccinated at a single hospital. Multicenter studies with a larger sample size are needed. In individuals with low antibody response to other viral vaccines, the mechanism by which humoral immunity is acquired after mRNA vaccination needs to be clarified through future research. In conclusion, after two doses of the BNT162b2 vaccine, both low and normal responders to previous antiviral vaccines developed adequate levels of SARS-CoV-2 anti-spike and SARS-CoV-2 neutralizing antibodies to protect against SARS-CoV-2. However, both low and normal responders had lower SARS-CoV-2 anti-spike antibody levels in the fifth month than in the first month after receiving the second dose of BNT162b2 vaccine. Therefore, a third dose of BNT162b2 vaccine should be administered to all individuals, regardless of their antibody response to previous antiviral vaccines.

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  6. Version published to 10.1101/2021.12.26.21268358v1 on medRxiv