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 at 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 receptor blocking antibodies (ACE2R-Abs), antibodies to the receptor binding domain (RBD) of the virus and variants of concern (VOC) and ex vivo T cell responses were assessed in a sub cohort.

Results

All individuals (100%) had SARS-CoV-2 specific total antibodies and 94.2% of cohort 1 and 97.1% of cohort 2 had ACE2R-blocking Abs. There was no difference in antibody titres or positivity rates in different age groups in both cohorts. The ACE2R-blocking Abs (p<0.0001) 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 haemagglutination assay to the RBD of the ancestral virus and VOCs in cohort 1, while 53.6% to 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 IFNγ ELISpot responses above the positive threshold. The ACE2R-blocking antibodies and ex vivo IFNγ ELISpot responses at 12 weeks post-first dose, significantly correlated with levels 12 weeks post second dose (Spearman’s r=0.46, p=0.008) and (Spearman’s r=0.71, p<0.0001) respectively.

Conclusions

Both dosing schedules resulted in high levels of 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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