Broad neutralization against SARS-CoV-2 variants induced by a modified B.1.351 protein-based COVID-19 vaccine candidate

  1. Danmei Su
  2. Xinglin Li
  3. Cui He
  4. Xueqing Huang
  5. Meilin Chen
  6. Qiang Wang
  7. Wenchang Qin
  8. Ying Liang
  9. Rong Xu
  10. Jinhua Wu
  11. Peiwen Luo
  12. Xiaofang Yang
  13. Yilan Zeng
  14. Mei Luo
  15. Dongxia Luo
  16. David M Salisbury
  17. Donna Ambrosino
  18. George Siber
  19. Ralf Clemens
  20. Peng Liang
  21. Joshua G. Liang

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Abstract

Beginning in late 2020, the emergence and spread of multiple variant SARS-CoV-2 strains harboring mutations which may enable immune escape necessitates the rapid evaluation of second generation COVID-19 vaccines, with the goal of inducing optimized immune responses that are broadly protective. Here we demonstrate in a mouse immunogenicity study that two doses of a modified B.1.351 spike (S)-Trimer vaccine (B.1.351 S-Trimer) candidate can induce strong humoral immune responses that can broadly neutralize both the original SARS-CoV-2 strain (Wuhan-Hu-1) and Variants of Concern (VOCs), including the UK variant (B.1.1.7), South African variant (B.1.351) and Brazil variant (P.1). Furthermore, while immunization with two doses (prime-boost) of Prototype S-Trimer vaccine (based on the original SARS-CoV-2 strain) induced lower levels of cross-reactive neutralization against the B.1.351 variant, a third dose (booster) administered with either Prototype S-Trimer or B.1.351 S-Trimer was able to increase neutralizing antibody titers against B.1.351 to levels comparable to neutralizing antibody titers against the original strain elicited by two doses of Prototype S-Trimer.

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  1. ScreenIT

    SciScore for 10.1101/2021.05.16.444369: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: All mouse experiments were approved by the institutional animal care and use committee (IACUC) in Clover Biopharmaceuticals and were conducted according to international guidelines for animal studies.
    IRB: Human COVID-19 convalescent serum samples: Human convalescent sera samples from recovered COVID-19 patients (table S1) infected with the original SARS-CoV-2 strain 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 sera sample were collected.
    Consent: Human COVID-19 convalescent serum samples: Human convalescent sera samples from recovered COVID-19 patients (table S1) infected with the original SARS-CoV-2 strain 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 sera 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 Beijing Vital River Laboratory Animal Technology Co., Ltd. and kept under standard pathogen-free conditions in the animal care center at Chengdu Hi-tech Incubation Park.
    Randomization2C) of the study, animals in group 1 were randomized to receive a booster (Dose 3 on Day 35) with either 3 µg Prototype or 3 µg B.1.351 S -Trimer (half adjuvanted and half non-adjuvanted).
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    After washing 3 times with PBST, the plates were incubated with 1:5000 dilution of rabbit anti-Trimer-Tag antibody (Clover Biopharmaceuticals) at 37°C for 1 h, followed by washing 3 times with PBST and then a 1:20000 dilution of goat anti-rabbit IgG-HRP (Southern Biotech).
    anti-Trimer-Tag
    suggested: None
    anti-rabbit IgG-HRP
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    After transient transfection in 293F cells, the variant S-Trimer antigens were expressed and secreted at sufficient levels to enable further characterization and mouse immunogenicity studies.
    293F
    suggested: RRID:CVCL_D615)
    Experimental Models: Organisms/Strains
    SentencesResources
    Animal studies, facilities and ethics statements: Specific pathogen-free (SPF) BALB/c female mice (6-8 weeks old) for immunogenicity studies were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. and kept under standard pathogen-free conditions in the animal care center at Chengdu Hi-tech Incubation Park.
    BALB/c
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Data arrangement was performed by Excel and statistical analyses were performed using the Prism 8.0 (GraphPad Software).
    Excel
    suggested: None
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    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: 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.

  2. Version published to 10.1101/2021.05.16.444369v1 on bioRxiv