A third COVID-19 vaccine shot markedly boosts neutralizing antibody potency and breadth

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Abstract

COVID-19 (coronavirus disease 2019) vaccines have been rapidly developed and deployed globally as a measure to combat the disease. These vaccines have been demonstrated to confer significant protection, but there have been reports of temporal decay in antibody titer. Furthermore, several variants have been identified with variable degrees of antibody resistance. These two factors suggest that a booster vaccination may be worthy of consideration. While such a booster dose has been studied as a series of three homologous vaccines in healthy individuals, to our knowledge, information on a heterologous regimen remains unreported, despite the practical benefits of such a scheme. Here, in this observational study, we investigated the serological profile of four healthy individuals who received two doses of the BNT162b2 vaccine, followed by a third booster dose with the Ad26.COV2.S vaccine. We found that while all individuals had spike-binding antibodies at each of the timepoints tested, there was an appreciable drop in titer by four months following the second vaccination. The third vaccine dose robustly increased titers beyond that of two vaccinations, and these elicited antibodies had neutralizing capability against all SARS-CoV-2 strains tested in both a recombinant vesicular stomatitis virus-based pseudovirus assay and an authentic SARS-CoV-2 assay, except for one individual against B.1.351 in the latter assay. Thus, a third COVID-19 vaccine dose in healthy individuals promoted not just neutralizing antibody potency, but also induced breadth against dominant SARS-CoV-2 variants.

Significance

COVID-19 vaccines confer protection from symptomatic disease, but the elicited antibody titer has been found to decrease with time. Furthermore, SARS-CoV-2 variants with relative resistance against antibody neutralization have been identified. To overcome such issues, a third vaccine dose applied as a booster vaccine may be necessary. We studied four healthy individuals who received a heterologous booster dose as a third vaccine. All of these individuals had heightened neutralizing antibody titer following the booster vaccination, and could neutralize nearly all variants tested. Thus, a heterologous third COVID-19 vaccine dose may be a mechanism to both heighten and broaden antibody titers, and could be an additional strategy for controlling the SARS-CoV-2 pandemic.

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  1. SciScore for 10.1101/2021.08.11.21261670: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was reviewed and approved by the Institutional Review Board of Columbia University.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Enzyme-linked immunosorbent assay (ELISA) to quantify anti-SARS-CoV-2 spike and nucleoprotein antibodies, recombinant vesicular stomatitis virus-based SARS-CoV-2 pseudovirus neutralization assay, and authentic SARS-CoV-2 neutralization assay, were performed as previously described (15).
    anti-SARS-CoV-2 spike and nucleoprotein
    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
    NCT04367857RecruitingARMOR Study: COVID-19 Seroprevalence Among Healthcare Worker…


    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.