Protection from Omicron and other VOCs by Bivalent S-Trimer COVID-19 Vaccine

  1. Danmei Su
  2. Xinglin Li
  3. Xueqin Huang
  4. Cui He
  5. Cheng Zeng
  6. Qiang Wang
  7. Wenchang Qin
  8. Zhongquan Mu
  9. Donna Ambrosino
  10. George Siber
  11. Ralf Clemens
  12. Joshua G. Liang
  13. Peng Liang
  14. Nick Jackson
  15. Rong Xu

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Abstract

The Omicron variant of SARS-COV-2 (GISAID GRA clade [B.1.1.529, BA.1 and BA.2]) is now the single dominant Variant of Concern (VOC). The high number of mutations in the Omicron Spike (S) protein promotes humoral immunological escape. Although a third homologous boost with S, derived from the ancestral strain, was able to increase neutralizing antibody titers and breadth including to Omicron, the magnitude of virus neutralization could benefit from further optimization. Moreover, combining SARS-COV-2 strains as additional valences may address the current antigenicity range occupied by VOCs.

Using Trimer-Tag™ platform we have previously demonstrated phase 3 efficacy and safety of a prototypic vaccine SCB-2019 in the SPECTRA trial and have submitted applications for licensure. Here, we successfully generated a bivalent vaccine candidate including both Ancestor and Omicron variant S-proteins. Preclinical studies demonstrate this SARS-CoV-2 bivalent S-Trimer subunit vaccine elicits high titers of neutralizing antibodies against all VOCs, with markedly enhanced Omicron specific neutralizing antibody responses.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.03.490428: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Human convalescent serum samples: Human convalescent serum samples from recovered COVID-19 patients were obtained from Public Health Clinical Center of Chengdu in Chengdu, China, under approved guidelines by the Institutional Review Board (IRB), and all patients had provided written informed consent before serum sample were collected.
    Consent: Human convalescent serum samples: Human convalescent serum samples from recovered COVID-19 patients were obtained from Public Health Clinical Center of Chengdu in Chengdu, China, under approved guidelines by the Institutional Review Board (IRB), and all patients had provided written informed consent before serum sample were collected.
    Sex as a biological variableAnimal studies, facilities and ethics statements: Specific pathogen-free (SPF) BALB/c female mice (6-8 weeks old) for immunogenicity studies were purchased from Charles River Experimental Animals Co.,
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serum was collected on D35 (2 weeks PD2), D56 (Day of 3rd dose boost), D85 (1 month post dose 3), D113 (2 months post dose3) and D141 (3 months post dose 3) for pseudovirus neutralizing antibody test.
    D56
    suggested: None
    D85
    suggested: None
    D113
    suggested: None
    D141
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Pseudovirions were produced by co-transfection HEK 293T cells with psPAX2, pLVX-AcGFP-N1-Fluc, and plasmids encoding various S genes by using Lipofectamine 3000 (Invitrogen, L3000-015).
    HEK 293T
    suggested: None
    Pseudoviruses stock were titrated by infecting 293T-ACE2 cells and luciferase activity was determined following a 44-48 h incubation period at 37°C and 5% CO2 by addition Bright-Glo Luciferase Assay System (Promega, E2650) using a microplate reader (TECAN, Spark).
    293T-ACE2
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    For three dose boost study, Balb/c mice, female (n=10/group) prime and boost with SCB-2019 3 μg adjuvanted with 75 μg alum plus 150 μg CpG 1018 twice on Day 0 and Day 21, then boosted with 3 μg SCB-2019, or SCB-2022B or Bivalent adjuvanted with 75 μg alum plus 150 μg CpG 1018 on Day 57 via intramuscular injection.
    Balb/c
    suggested: None
    Recombinant DNA
    SentencesResources
    The cDNA was subcloned into pTRIMER expression vector (GenHunter Corporation) at Hind III and Bgl II sites to allow in-frame fusion of the soluble S protein to Trimer-Tag (amino acid residue 1156-1406 from human Type I(α) collagen).
    pTRIMER
    suggested: None
    Pseudovirus construction and production: The variants of concern of SARS-CoV-2 spike protein genes were optimized using mammalian codon and synthesized by Genscript, then cloned into pcDNA3.1(+) eukaryotic expression vector.
    pcDNA3.1
    suggested: RRID:Addgene_79663)
    Pseudovirions were produced by co-transfection HEK 293T cells with psPAX2, pLVX-AcGFP-N1-Fluc, and plasmids encoding various S genes by using Lipofectamine 3000 (Invitrogen, L3000-015).
    psPAX2
    suggested: RRID:Addgene_12260)
    pLVX-AcGFP-N1-Fluc
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Data arrangement was performed by Excel and statistical analyses were performed using the Prism 9.2.0 (GraphPad Software).
    Excel
    suggested: None
    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: 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
    NCT04405908CompletedSCB-2019 as COVID-19 Vaccine
    NCT04672395RecruitingA Controlled Phase 2/3 Study of Adjuvanted Recombinant SARS-…

    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 10.1101/2022.05.03.490428v1 on bioRxiv