Immunogenicity and safety of the homogenous booster shot of a recombinant fusion protein vaccine (V-01) against COVID-19 in healthy adult participants primed with a two-dose regimen

  1. Yuan Li
  2. Xin Fang
  3. Rongjuan Pei
  4. Renfeng Fan
  5. Shaomin Chen
  6. Peiyu Zeng
  7. Zhiqiang Ou
  8. Jinglong Deng
  9. Jian Zhou
  10. Zehui Sun
  11. Lishi Liu
  12. Hua Peng
  13. Xujia Chen
  14. Zhipeng Su
  15. Xi Chen
  16. Jianfeng He
  17. Wuxiang Guan
  18. Zhongyu Hu
  19. Yang-Xin Fu
  20. Jikai Zhang

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Abstract

Background

Rising concerns over waning immunity and reduction in neutralizing activity against variants of concern (VOCs) have contributed to deploying booster doses by different strategies to tackle the COVID-19 pandemic. Preliminary findings from Phase I and II have shown that V-01, a recombinant fusion protein vaccine against COVID-19, exhibited favorable safety and immunogenicity profiles in 1060 adult participants of both younger and senior age. Herein, we aimed to assess the immunogenicity and safety for a booster dose in participants previously primed with a two-dose 10μg V-01 regimen (day 0, 21) from phase I trial, providing reassuring data for necessity and feasibility of a homogenous booster dose.

Methods

We conducted a single-arm, open-label trial at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China). Forty-three eligible participants who were previously primed 4-5 months earlier with two-dose 10μg V-01 regimen from phase I trial received booster vaccination. We primarily assessed the immunogenicity post-booster vaccination, measured by RBD-binding antibodies using ELISA and neutralizing activity against wild-type SARS-CoV-2 and emerging variants of concern (VOCs) using neutralization assays. We secondarily assessed the safety and reactogenicity of the booster vaccination.

Results

The third dose of V-01 exhibited significant boosting effects of humoral immune response in participants primed with two-dose 10μg V-01 regimen regarding both wild-type SARS-CoV-2 and VOCs. We observed a 60.4-folds increase in neutralizing titres against SARS-CoV-2 of younger adults, with GMTs of 17 (95%CI: 12-23) prior to booster vaccination in comparison to 1017 (95%CI: 732-1413) at day 14 post booster vaccination; and a 53.6-folds increase in that of older adults, with GMTs of 14 (95%CI: 9-20) before booster vaccination in comparison to 729(95%CI: 397-1339) at day 14 post-booster vaccination. The neutralizing titres against SARS-CoV-2 Delta strain also demonstrated a sharp increase from the day of pre booster vaccination to day 14 post booster vaccination, with GMTs of 11 (95%CI:8-15) versus 383 (95%CI:277-531) in younger adults (35.4-folds increase), and 6.5(95%CI: 5-8) versus 300(95%CI:142-631) in older adults (46.0-folds increase), respectively. We also observed a considerable and consistent increase of pseudovirus neutralizing titres against emerging VOCs from day 28 post second vaccination to day 14 post booster vaccination, with GMTs of 206 (95%CI:163-259) versus 607 (95%CI: 478-771) for Alpha strain, 54 (95%CI:38-77) versus 329 (95%CI: 255-425) for Beta strain, 219 (95%CI:157-306) versus 647 (95%CI: 484-865) for Delta strain. Our preliminary findings indicate a homogenous booster dose of V-01 was safe and well-tolerated, with overall adverse reactions being absent or mild-to-moderate in severity, and no grade 3 or worse AEs were related to booster vaccination.

Conclusions

A homogenous booster immunization in participants receiving a primary series of two-dose V-01 elicited a substantial humoral immune response against wild-type SARS-CoV-2 and emerging VOCs, along with a favorable safety and reactogenicity profile. Our study provided promising data for a homogenous prime-boost strategy using recombinant protein vaccine to tackle the ongoing pandemic, potentially providing broad protection against emerging VOCs and overcoming waning immunity.

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  1. ScreenIT

    SciScore for 10.1101/2021.11.04.21265780: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Written informed consent of each participant was obtained prior to the booster vaccination.
    IRB: The trial protocol was reviewed and approved by the Institutional Review Board of the Guangdong Provincial Center of Disease Control and Prevention.
    Sex as a biological variableEligible participants were those who completed the initial two-dose regimens of 10μg V-01 in phase I trial25 4-5 months earlier and who did not meet the withdrawal criteria, voluntarily consented to participate in this trial, agreed to take effective contraceptive measures (women of childbearing potential) during the study, and without a history of SARS-CoV-2 infection or close contact to asymptomatic individuals.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The immunogenicity outcomes were geometric mean titer (GMT), geometric mean increases (GMI) of the RBD-binding antibody, and SARS-CoV-2 neutralizing antibody.
    SARS-CoV-2 neutralizing antibody.
    suggested: None
    The GMTs with associated Clopper-Pearson 95% CIs for the neutralizing and RBD-binding antibodies against wild-type SARS-CoV-2 were calculated.
    antibodies against wild-type SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Analyses were conducted using SAS 9.4 (SAS Institute Inc
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)
    ., San Diego, CA, USA), then graphed using GraphPad Prism 8.0 (GraphPad Software Inc.
    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:
    The study has several limitations: (1) the administration interval between the booster dose and the second dose all ranged within 4-5 months, which might need a broader spectrum of range and further stratification for roll-out timing for booster doses. From public health perspective, the optimal timing of booster shot after prime immunization should consider multiple factors, including the current prevalence of COVID-19, supply of COVID-19 vaccine, emerging VOCs epidemiology, etc. (2) cross-neutralizing panels at day 28 after second vaccination who received a two-dose 10μg V-01 regimen in phase II was different from the cohorts receiving a booster dose. As a consequence, the comparison of cross-neutralizing activities against variants between primary two-dose series and booster vaccination should be interpreted with caution. (3) the sample size is relatively small, which is insufficient to assess rare vaccine-related AEs. (4) The long-term safety data of current cohorts in phase I trial was terminated since the application of the booster shots, and the T-cell immunity has not yet been analyzed. In conclusion, the booster dose of V-01 in participants previously primed with 21d-apart two-dose 10μg V-01 in phase I trial elicited potent humoral response against both wild-type and Delta strain of SARS-CoV-2 and exhibited a favorable and well-tolerated safety profile. Albeit a substantial decline of immunity was observed between 14 days post-second dosing and pre-booster dosing, hu...

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

    IdentifierStatusTitle
    NCT05050474Active, not recruitingBooster Immunization Study of Recombinant SARS-CoV-2 Fusion …

    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.

  2. Version published to 10.1101/2021.11.04.21265780v1 on medRxiv