Heterologous vaccination strategy for containing COVID-19 pandemic

  1. Ang Lin
  2. JingJing Liu
  3. Xiaopin Ma
  4. Fanfan Zhao
  5. Bo Yu
  6. Jiaxin He
  7. Mingyun Shen
  8. Lei Huang
  9. Hongming Tang
  10. Erpeng Jiang
  11. Yue Wang
  12. Pingfang Cui
  13. Yujian Zhang
  14. Weiguo Yao
  15. Aihua Zhang
  16. Youchun Wang
  17. Yuhua Li
  18. Weijin Huang
  19. Qihan Li
  20. Zhongmin Liu
  21. Hangwen Li

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

An unequitable vaccine allocation and continuously emerging SARS-CoV-2 variants pose challenges to contain the pandemic, which underscores the need for licensing more vaccine candidates, increasing manufacturing capacity and implementing better immunization strategy. Here, we report data from a proof-of-concept investigation in two healthy individuals who received two doses of inactivated whole-virus COVID-19 vaccines, followed by a single heterologous boost vaccination after 7 months with an mRNA vaccine candidate (LPP-Spike-mRNA) developed by Stemirna Therapeutics. Following the boost, Spike-specific antibody (Ab), memory B cell and T cell responses were significantly increased. These findings indicate that a heterologous immunization strategy combining inactivated and mRNA vaccines can generate robust vaccine responses and therefore provide a rational and effective vaccination regimen.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.05.17.21257134: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: Study subjects, immunization and sample collection: This study was approved by the local ethical committee at Tongji University East Hospital, Shanghai, China, and was performed according to the Declaration of Helsinki Principles.
    Consent: Two subjects were enrolled in this study and gave written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody cocktail contains the following fluorescently-labelled antibodies: anti- human CD3 Ab (clone: SP34-2)
    anti- human CD3
    suggested: (BD Biosciences Cat# 552127, RRID:AB_394342)
    Experimental Models: Cell Lines
    SentencesResources
    pVNT assay was performed as previously reported9 where in-house constructed vesicular stomatitis virus (VSV) expressing SARS-CoV-2 Spike protein (strain Wuhan-Hu-1) is used to infect ACE2-expressing Huh7 cells.
    Huh7
    suggested: CLS Cat# 300156/p7178_HuH7, RRID:CVCL_0336)
    Software and Algorithms
    SentencesResources
    Data were analyzed using FlowJo V.10.1 (Tree Star)
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)

    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:
    Therefore, heterologous vaccination strategy holds the prospect for augmenting vaccine efficacy.The limitation in our study is the lack of control subjects receiving a homologous booster with the same inactivated vaccine for a side-by-side comparison. Therefore the findings we presented here remain to be further validated in large cohort of subjects. In addition, other parameters need to be investigated in the context of heterologous COVID-19 vaccination, for example different vaccine types, order of vaccine administration, interval between priming and booster, and number of doses. A very recently initiated clinical trial (ClinicalTrial.gov: NCT04833101) aiming to study the outcomes of heterologous COVID- 19 vaccination using a viral-vector based and a RBD-based subunit vaccine will offer a good opportunity for further investigations on this topic.

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

    IdentifierStatusTitle
    NCT04412538RecruitingSafety and Immunogenicity Study of an Inactivated SARS-CoV-2…
    NCT04659239Enrolling by invitationThe Efficacy, Safety and Immunogenicity Study of Inactivated…
    NCT04833101Active, not recruitingStudy on Sequential Immunization of Recombinant COVID-19 Vac…

    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 10.1101/2021.05.17.21257134v1 on medRxiv