Immune responses following 3rd and 4th doses of heterologous and homologous COVID-19 vaccines in kidney transplant recipients

  1. Tina Thomson
  2. Maria Prendecki
  3. Sarah Gleeson
  4. Paul Martin
  5. Katrina J Spensley
  6. Rute Cardoso De Aguiar
  7. Bynvant Sandhu
  8. Charlotte Seneschall
  9. Jaslyn Gan
  10. Candice L. Clarke
  11. Shanice Lewis
  12. Graham Pickard
  13. David Thomas
  14. Stephen P. McAdoo
  15. Liz Lightstone
  16. Alison Cox
  17. Peter Kelleher
  18. Michelle Willicombe
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Abstract

Background

Solid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. In this study, we report on immune responses to 3rd- (V3) and 4th- (V4) doses of heterologous and homologous vaccines in a kidney transplant population.

Methods

724 kidney transplant recipients were prospectively screened for serological responses following 3 primary doses of a SARS-CoV2 vaccine. 322 patients were sampled post-V4 for anti-spike (anti-S), with 69 undergoing assessment of SARS-CoV-2 T-cell responses. All vaccine doses were received post-transplant, only mRNA vaccines were used for V3 and V4 dosing. All participants had serological testing performed post-V2 and at least once prior to their 1st dose of vaccine.

Results

586/724 (80.9%) patients were infection-naïve post-V3; 141/2586 (24.1%) remained seronegative at 31 (21-51) days post-V3. Timing of vaccination in relation to transplantation, OR: 0.28 (0.15-0.54), p=0.0001; immunosuppression burden, OR: 0.22 (0.13-0.37), p<0.0001, and a diagnosis of diabetes, OR: 0.49 (0.32-0.75), p=0.001, remained independent risk factors for non-seroconversion. Seropositive patients post-V3 had greater anti-S if primed with BNT162b2 compared with ChAdOx1, p=0.001.

Post-V4, 45/239 (18.8%) infection-naïve patients remained seronegative. De novo seroconversion post-V4 occurred in 15/60 (25.0%) patients who were seronegative post-V3. There was no difference in anti-S post-V4 by vaccine combination, p=0.50. Anti-S post-V4 were sequentially greater in those seroconverting post V2- compared with V3-, and V3- compared with V4-, at 1561 (567-5211), 379 (101-851) and 19 (9.7-48) BAU/ml respectively.

T-cell responses were poor, with only 11/54 (20.4%) infection-naive patients having detectable T-cell responses post-V4, with no difference seen by vaccine type.

Conclusion

A significant proportion of transplant recipients remain seronegative following 3- and 4- doses of SARS-CoV-2 vaccines, with poor T-cell responses, and are likely to have inadequate protection against infection.

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