Inactivated whole-virion vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern

  1. Rajesh Vikkurthi
  2. Asgar Ansari
  3. Anupama R. Pai
  4. Someshwar Nath Jha
  5. Shilpa Sachan
  6. Suvechchha Pandit
  7. Bhushan Nikam
  8. Anurag Kalia
  9. Bimal Prasad Jit
  10. Hilal Ahmad Parray
  11. Savita Singh
  12. Pallavi Kshetrapal
  13. Nitya Wadhwa
  14. Tripti Shrivastava
  15. Poonam Coshic
  16. Suresh Kumar
  17. Pragya Sharma
  18. Nandini Sharma
  19. Juhi Taneja
  20. Anil K. Pandey
  21. Ashok Sharma
  22. Ramachandran Thiruvengadam
  23. Alba Grifoni
  24. Daniela Weiskopf
  25. Alessandro Sette
  26. Shinjini Bhatnagar
  27. Nimesh Gupta

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Abstract

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  1. Version published to 10.1038/s41564-022-01161-5
  2. ScreenIT

    SciScore for 10.1101/2021.11.14.21266294: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics Statement: The study protocols were approved by the Human Research Ethics Committees of National Institute of Immunology and the partnering institutions.
    Consent: All participants provided written informed consent before enrolment for the study.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The sample absorbance was inversely proportional to the titre of the anti-SARS-CoV-2 neutralizing antibodies.
    anti-SARS-CoV-2 neutralizing antibodies .
    suggested: None
    For detection of antibody secreting cell (ASC) spots corresponding to IgG+, IgM+ and IgA+ isotype, the plate was developed using detection monoclonal anti-human antibodies; IgG-550 (MT78/145), IgM-640 (MT22) and IgA-490 (MT20), diluted 1:500 in PBS containing 0.5% FBS for 2 hours in dark at room temperature.
    IgG+ , IgM+ and IgA+
    suggested: None
    anti-human antibodies; IgG-550
    suggested: None
    IgM-640 ( MT22
    suggested: None
    IgA-490
    suggested: None
    MT20
    suggested: None
    After the stimulation period, cells were washed with FACS buffer (2% FBS in PBS) and surface stained with monoclonal antibody cocktail for 1 hour at 4 C in the dark; CD20, CD14, CD16, CD8a and fixable-viability dye coupled with APC eflour 780 in the dump channel, CD4-AlexaFluor 700 (RPA-T4), OX40-FITC (Ber-ACT35)
    CD20
    suggested: (BioLegend Cat# 348805, RRID:AB_2889063)
    CD14
    suggested: (BioLegend Cat# 348805, RRID:AB_2889063)
    CD16
    suggested: None
    Briefly, cryopreserved PBMCs were revived as mentioned previously with ≥90% cellular viability and surface stained with following monoclonal antibodies for 15 minutes at 4 °C: fixable viability dye efluor 506, anti-CD4 AF700 (RPA-T4)
    anti-CD4
    suggested: (SouthernBiotech Cat# 1540-27, RRID:AB_2794844)
    After incubation, IFN-γ spots were detected using BAM conjugated monoclonal antibody against IFN-γ (7-B6-1-BAM, Mabtech, Sweden).
    antibody against IFN-γ (7-B6-1-BAM, Mabtech, Sweden).
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The sequence verified plasmid DNA representing mutant as well as wild type RBD sequences was further transfected to Expi293 cells using ExpiFectamine 293 Transfection Kit (ThermoFisher), and the secreted protein was purified from the supernatant.
    Expi293
    suggested: RRID:CVCL_D615)
    Software and Algorithms
    SentencesResources
    For all analyses, after staining, cells were washed and fixed with freshly prepared 1% Paraformaldehyde (Sigma Aldrich) followed by acquiring using BD LSRFortessa X-20 flow cytometer (BD Biosciences) and subsequent data analysis by FlowJo 10.7.1.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analyses and data visualization were performed with the GraphPad Prism software version v8.4.3.
    GraphPad Prism
    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:
    Limitations of this study includes a modest sample size and limited blood volume to perform simultaneous analyses of multiple cellular responses to SARS-CoV-2 and VOCs. Although, the analyses from 4 weeks post-2nd dose up to 6 months suffice for key information on the persistence of immune memory, the durability of immune memory cannot be defined in the absence of analyses at the baseline and the longitudinal follow up. The detailed immunological investigation in the larger prospective cohort of vaccine effectiveness is required for identifying the immune correlates-of-protection and understanding the mechanism of protective immunity conferred by BBV152. BBV152-induced protective immunity seems to comprise of a low magnitude of neutralizing antibodies with potent T-cell response and a larger breadth of cellular reactivity against variants. The effective presence of memory T cells and antibodies in the respiratory tract will be ideal to control not only the SARS-CoV-2 infection but also the disease transmission. Thus, it’ll be worth investigating if BBV152 booster immunization via intranasal route can mediate localization of the protective immune memory in the local sites of infection or upper respiratory tract. With the encouraging demonstration of the potential of BBV152 in generating immune memory and its effectiveness against the recent virus variants, our study provides an assuring foundation for the future application of BBV152, an adjuvanted inactivated virus vaccine, i...

    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.

  3. Version published to 10.1101/2021.11.14.21266294v1 on medRxiv