Serendipitous COVID-19 Vaccine-Mix in Uttar Pradesh, India: Safety and Immunogenicity Assessment of a Heterologous Regime

  1. Rajni Kant
  2. Gaurav Dwivedi
  3. Kamran Zaman
  4. Rima R Sahay
  5. Gajanan Sapkal
  6. Himanshu Kaushal
  7. Dimpal A. Nyayanit
  8. Pragya D Yadav
  9. Gururaj Deshpande
  10. Rajeev Singh
  11. Sandeep Chaowdhary
  12. Nivedita Gupta
  13. Sanjay Kumar
  14. Priya Abraham
  15. Samiran Panda
  16. Balram Bhargava

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Abstract

Immunization program against COVID-19 in India started with two vaccines; AstraZeneca’s ChAdOx1-nCov-19 (termed Covishield in India) and inactivated whole virion BBV152 (Covaxin); homologous prime-boost approach was followed. However, eighteen individuals, under the national program, inadvertently received Covishield as the first jab and Covaxin as the second. We compared the safety and immunogenicity profile of them against that of individuals receiving either Covishield or Covaxin (n=40 in each group). Lower and similar adverse events following immunization in all three groups underlined the safety of the combination vaccine-regime. Immunogenicity profile against Alpha, Beta and Delta variants in heterologous group was superior; IgG antibody and neutralising antibody response of the participants was also significantly higher compared to that in the homologous groups. The findings suggest that immunization with a combination of an adenovirus vector platform-based vaccine followed by an inactivated whole virus vaccine was not only safe but also elicited better immunogenicity.

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  1. Version published to 10.1101/2021.08.06.21261716v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.08.06.21261716: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethical statement: The study was approved by the Institutional Ethics Committee of the ICMR-Regional Medical Research Centre (ICMR-RMRC), Gorakhpur (IHEC Number-RMRCGKP/EC/2021/2.1).
    Consent: Written and informed consent was obtained from all the participants enrolled in the study before the collection of clinical data and samples.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    , Nucleocapsid (N) protein, inactivated whole SARS-CoV-2 antigen, neutralizing antibody (NAb) response and phenotyping of lymphoid cells of lysed whole blood.
    Nucleocapsid ( N ) protein , inactivated whole SARS-CoV-2 antigen ,
    suggested: None
    Anti-SARS-CoV-2 IgG antibody evaluation: We evaluated anti-SARS-CoV-2 IgG antibody response against S1-RBD, N-protein and the whole antigen.
    anti-SARS-CoV-2 IgG
    suggested: None
    S1-RBD , N-protein and the whole antigen .
    suggested: None
    Anti-SARS-CoV-2 antibody (NIBSC code 20/130) was also included in the assay as a reference standard.
    Anti-SARS-CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Post incubation at 37°C for 1 hr, each virus-diluted serum sample (0.1 ml) was inoculated onto duplicate wells of a 24-well tissue culture plate of Vero CCL-81 cells.
    Vero CCL-81
    suggested: None
    Software and Algorithms
    SentencesResources
    The ELISA titres against S1-RBD, N protein and inactivated SARS-CoV-2 (whole virus) was compared in sera of the three groups and analysed statistically using the Kruskal-Wallis test along with Dunns’ multiple comparisons in GraphPad Prism.
    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:
    There are a few limitations in our study. The sample size of 18 participants is small, the follow up period is only 60-70 days after immunisation with the first dose and baseline serological and immunological data of the participants is not available. However, there are several major strengths in this study. This is the first report of heterologous immunisation with an adenovirus vector based and an inactivated whole virion vaccine in humans demonstrating safety and significantly improved immunogenicity. Qian He et al., had earlier reported similar findings in a mouse model9. Comparable proportion of solicited AEFIs in the heterologous and homologous groups despite the elderly age group (mean age 62 years) demonstrates the safety of combination regimen. Immunogenicity profile studied against the VOCs; Alpha, Beta and Delta variants demonstrates significantly higher titers in the heterologous group. Overall, this study demonstrates that immunization with a heterologous combination of an adenovirus vector platform-based vaccine followed by an inactivated whole virus vaccine is safe and elicits better immunogenicity than two doses of homologous vaccination, using the same vaccines. These findings have an important implication for the COVID-19 vaccination program wherein heterologous immunisation will pave the way for induction of improved and better protection against the variant strains of SARS-CoV-2. Such mixed regimens will also help to overcome the challenges of shortfall of...

    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 10.1101/2021.08.06.21261716v1 on medRxiv