Kinetics of immune responses to the AZD1222/Covishield vaccine with varying dose intervals in Sri Lankan individuals

  1. Chandima Jeewandara
  2. Inoka Sepali Aberathna
  3. Laksiri Gomes
  4. Pradeep Darshana Pushpakumara
  5. Saubhagya Danasekara
  6. Dinuka Guruge
  7. Thushali Ranasinghe
  8. Banuri Gunasekera
  9. Achala Kamaladasa
  10. Heshan Kuruppu
  11. Gayasha Somathilake
  12. Osanda Dissanayake
  13. Nayanathara Gamalath
  14. Dinithi Ekanayake
  15. Jeewantha Jayamali
  16. Deshni Jayathilaka
  17. Anushika Mudunkotuwa
  18. Michael Harvie
  19. Thashmi Nimasha
  20. Ruwan Wijayamuni
  21. Lisa Schimanski
  22. Pramila Rijal
  23. Tiong K. Tan
  24. Tao Dong
  25. Alain Townsend
  26. Graham S. Ogg
  27. Gathsaurie Neelika Malavige

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Abstract

Background

To understand the kinetics of immune responses with different dosing gaps of the AZD1222 vaccine, we compared antibody and T cell responses in two cohorts with two different dosing gaps.

Methods

Antibodies to the SARS‐CoV‐2 virus were assessed in 297 individuals with a dosing gap of 12 weeks, sampled 12 weeks post second dose (cohort 1) and in 77 individuals with a median dosing gap of 21.4 weeks (cohort 2) sampled 6 weeks post second dose. ACE2‐blocking antibodies (ACE2‐blocking Abs), antibodies to the receptor‐binding domain (RBD) of  variants of concern (VOC), and ex vivo T cell responses were assessed in a subcohort.

Results

All individuals (100%) had SARS‐CoV‐2‐specific total antibodies and 94.2% of cohort 1 and 97.1% of cohort 2 had ACE2‐blocking Abs. There was no difference in antibody titers or positivity rates in different age groups in both cohorts. The ACE2‐blocking Abs ( p  < .0001) and antibodies to the RBD of the VOCs were significantly higher in cohort 2 compared to cohort 1. 41.2% to 65.8% of different age groups gave a positive response by the hemagglutination assay to the RBD of the ancestral virus and VOCs in cohort 1, while 53.6%–90% gave a positive response in cohort 2. 17/57 (29.8%) of cohort 1 and 17/29 (58.6%) of cohort 2 had ex vivo interferon (IFN)γ ELISpot responses above the positive threshold. The ACE2‐blocking antibodies (Spearman's r  = .46, p  = .008) and ex vivo IFNγ responses (Spearman's r  = .71, p  < .0001) at 12 weeks post first dose, significantly correlated with levels 12 weeks post second dose.

Conclusions

Both dosing schedules resulted in high antibody and T cell responses post vaccination, although those with a longer dosing gap had a higher magnitude of responses, possibly as immune responses were measured 6 weeks post second dose compared to 12 weeks post second dose.

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  1. Version published to 10.1002/iid3.592
  2. ScreenIT

    SciScore for 10.1101/2021.10.27.21265561: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics approval was obtained from the Ethics Review Committee of University of Sri Jayewardenepura.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Detection of SARS-CoV-2 specific total antibodies: The presence of SARS-COV-2 specific total antibodies (IgM, IgA and IgG) were detected by using the Wantai SARS-CoV-2 Ab ELISA (Beijing Wantai Biological Pharmacy Enterprise, China), which detects antibodies to the receptor binding domain (RBD) of the spike protein.
    IgM, IgA
    suggested: None
    IgG
    suggested: None
    Assays to determine antibodies to the N protein: Qualitative detection of antibodies to SARS-CoV-2 nucleocapsid (N) antigen in human serum was performed using Elecsys® Anti-SARS-CoV-2 electrochemiluminescence immunoassay (Cat:
    SARS-CoV-2 nucleocapsid ( N )
    suggested: None
    Briefly, ELISpot plates (Millipore Corp., Bedford, USA) were coated with anti-human IFNγ antibody overnight (Mabtech, Sweden).
    anti-human IFNγ
    suggested: None

    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

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  3. Version published to 10.1101/2021.10.27.21265561v1 on medRxiv